CLINICAL TRIALS: A HISTORICAL PERSPECTIVE

Although there are many definitions for clinical trials, they are generally considered to be biomedical or health-related research studies in human beings that follow a pre-defined protocol. Carefully conducted clinical trials are the safest and fastest way to find treatments that work in people, and new ways to improve health. Many clinical trials are done to see if a new drug or device is safe and effective for people to use. These clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions.

In Phase I trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. In Phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety. In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely. In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

Developing countries like India and Latin American countries are becoming ideal destinations to conduct clinical trials. There are many reasons for this. Mainly, flexibility of the government rules, availability of large pool of patients, trained physicians, low capital input and reduced study period. However, the clinical trials in developing and under developed nations are reported to misuse the patients. In several cases, patients were not informed what for they are used. And there are media reports that many patients have suffered a lot due to clinical trials and even many were died.

But using human for research is not a recent issue. Several controversial studies have contributed to the development of regulations to protect human research participants. Here I am giving very few examples for this from the web pages.

Nazi Government Research: During Second World War prisoners in concentration camps were used as subjects in Nazi experiments designed to advance the war effort. The studies involved battlefield medicine and chemical warfare experiments in which prisoners were tortured, usually to death. As a result of the methods used to conduct the experiments, the physicians involved were put on trial by the International Military Tribunal in Nuremberg, Germany from October 1945 to October 1946. Additional trials conducted by United States judges appointed by President Truman were held from December 1946 to August 1947. Fifteen of the 23 defendants were convicted and seven were executed for murder, torture and other atrocities.

Willowbrook Hepatitis Study (Mid 1950s to Early 1970s): The Willowbrook study involved infecting mentally retarded children with a Hepatitis virus to study the progression of the disease and to test vaccinations that were being developed at the time. Due to overcrowding, children were denied entrance to the Willowbrook State Mental Hospital unless parents enrolled their children into the less-crowded hepatitis ward.

Tuskegee Syphilis Study: In 1932, the Public Health Service of United States of America enrolled several hundred syphilitic black males to document the effects of the untreated disease over time. Tuskegee was chosen because approximately 40% of the male population of the town was infected with the disease. Treatment was withheld from study subjects when penicillin was accepted as the treatment for syphilis in 1943. This study was stopped in 1973 but not before many subjects became seriously ill, transmitted their disease to others or died. This study exemplifies unfair subject selection practices, denial of informed consent and excessive risk in relation to study benefits.

Milgram Study (1963): The Milgram study involved instructing subjects to administer electric shocks to a study confederate in response to poor performance. The subject believed that he/she was involved in a study about learning and memory with each shock intended to affect the learning process. The confederate pretended to be hurt by the shock - in some cases, to the point of losing consciousness; however, he/she did not really feel any shock. The study objective was to assess obedience to authority. This study resulted in significant psychological stress for some subjects including sweating, trembling, stuttering and serious seizures in three subjects. However, in a post-experimental interview, about half of the subjects expressed that they were glad to have participated in the experiment. The question of whether this study was ethical remains open to debate among scholars today.

US human radiation experiments (1944-74): Thousands of experiments took place during the cold war era in which humans were exposed to dangerous levels of radiation to test the effects of the atomic bomb, to gather safety data on the effects of the atomic bomb and to develop treatments for cancer patients. . In many cases, subjects provided informed consent prior to their participation, however this was not the case for subjects who were sick, imprisoned or otherwise vulnerable, including 54 mentally retarded children who were intentionally fed radioactive breakfast cereal. In 1993, an advisory committee to former President Clinton apologized for conducting these experiments.

M. Jayaprakashvel
Research Scholar

ARTIFICIAL LETTERS ADDED TO LIFE'S ALPHABET

Two artificial DNA "letters" that are accurately and efficiently replicated by a natural enzyme have been created by US researchers. Adding the two artificial building blocks to the four that naturally comprise DNA could allow wildly different kinds of genetic engineering, they say. Eventually, the researchers say, they may be able to add them into the genetic code of living organisms.

The diversity of life on earth evolved using genetic code made from arrangements of four genetic "bases", sometimes described as letters. They are divided into two pairs, which bond together from opposite strands of a DNA molecule to form the rungs of its characteristic double-helix shape.

The unnatural but functional new base pair is the fruit of nearly a decade of research by chemical biologist Floyd Romesberg, at the Scripps Research Institute, La Jolla, California, US. Romesberg and colleagues painstakingly created a library of nearly 200 potential new genetic bases that are slight variations on the natural ones. Unfortunately, none of them were similar enough in structure and chemistry to the real thing to be copied accurately by the polymerase enzymes that replicate DNA inside cells.

Random generation
Frustrated by the slow pace designing and synthesising potential new bases one at a time, Romesberg borrowed some tricks from drug development companies. The resulting large scale experiments generated many potential bases at random, which were then screened to see if they would be treated normally by a polymerase enzyme.

With the help of graduate student Aaron Leconte, the group synthesized and screened 3600 candidates. Two different screening approaches turned up the same pair of molecules, called dSICS and dMMO2. The molecular pair that worked surprised Romesberg. "We got it and said, 'Wow!' It would have been very difficult to have designed that pair rationally”. But the team still faced a challenge. The dSICS base paired with itself more readily than with its intended partner, so the group made minor chemical tweaks until the new compounds behaved properly.

Novel DNA
“We probably made 15 modifications,” says Romesberg, “and 14 made it worse”. Sticking a carbon atom attached to three hydrogen atoms onto the side of dSICS, changing it to d5SICS, finally solved the problem. "We now have an unnatural base pair that's efficiently replicated and doesn't need an unnatural polymerase," says Romesberg. “It's staring to behave like a real base pair”. The team is now eager to find out just what makes it work. "We still don't have a detailed understanding of how replication happens”, says Romesberg. “Now that we have an unnatural base pair, we are continuing experiments to understand it better”.

In the near future, Romesberg expects the new base pairs will be used to synthesize DNA with novel and unnatural properties. These might include highly specific primers for DNA amplification; tags for materials, such as explosives, that could be detected without risk of contamination from natural DNA; and building novel DNA-based nanomaterials.
Increased 'evolvability'

More generally, Romesberg notes that DNA and RNA are now being used for hundreds of purposes: for example, to build complex shapes, build complex nanostructures, silence disease genes, or even perform calculations. A new, unnatural, base pair could multiply and diversify these applications.

The most challenging goal, says Romesberg, will be to incorporate unnatural base pairs into the genetic code of organisms. “We want to import these into a cell, study RNA trafficking, and in the longest term, expand the genetic code and 'evolvability' of an organism”.

Journal reference: Journal of the American Chemical Society
Published on Web 25 Jan 2008. Discovery, Characterization, and Optimization of an Unnatural Base Pair for Expansion of the Genetic Alphabet
Aaron M. Leconte, Gil Tae Hwang, Shigeo Matsuda, Petr Capek,
Yoshiyuki Hari, and Floyd E. Romesberg
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, U.S.A.

News Compiled by
Prof.N.Raaman
Centre for Advanced Studies in Botany
University of Madras, Guindy Campus
Chennai-600 025
Email:raaman55@gmail.com

NANOBES

Nanobes are tiny filamental structures first found in some rocks and sediments. Some hypothesize that they are the smallest form of life, ten times smaller than the smallest known bacteria.

Nanobes were discovered in 1996 (published in American Minerologist, vol 83., 1998) by Philipa Uwins, University of Queensland, Australia.

The smallest are just 20 nanometers in diameter. Some researchers believe them to be merely crystal growths, but a purported find of DNA in nanobe samples may prove otherwise. They are similar to the life-like structures found in ALH84001, the famous Mars meteorite from the Antarctic. Recently there has been some interest amongst bio-tech companies in commercial application of nanobes in utilization of plastics. Some researchers believe nanobe-like organisms might be implicated in a number of diseases. They might be responsible for the formation of some types of renal stones. They might even explain mysterious calcification of teeth in the human mouth, and thus actually be a useful or necessary symbiont (like Acidophilus).Although nanobacteria are sometimes called nanobes, it has not yet been confirmed that the names "nanobacteria" and "nanobes" could in fact be considered as synonyms, as both entities are controversial and are still under research.

Claims

It is a living organism (contains DNA or some analogue, and reproduces).

Has a morphology similar to Actinomycetes and Fungi.

No article or research states that Nanobes are Nanobacteria.

Nanobes are 20 nm in length which biological conventional wisdom assumes is too small to contain the basic elements for an organism to exist (DNA, plasmids, etc.), suggesting that they may reproduce via some unconventional means, like RNA instead of DNA.

The Martian meteorite ALH84001, discovered in 1996 in the Antarctic, contained similar tubular structures which some astrobiologists suggest could be proof of life at an earlier time on Mars.


GAYATHRI V

I MSc INDUSTRIAL MICROBIOLOGY

AMAZING HUMAN FACTS

The average human brain has about 100 billion nerve cells.
The only jointless bone in our body is the hyoid bone in the throat.
It is impossible to sneeze with our eyes open.
The average life of taste buds is 10 days.
Human thigh bones are stronger than concrete.
When we sneeze all our body functions stop, even our heart[0.1 micro second].
Children grow faster in the spring time.
Women blink nearly twice as much as men.
Our ears & nose continue to grow throughout our entire life.
A human being loses an average of 40-100 strands of hair a day.
A foetus acquires finger prints at the age of three months.
Every person has a unique tongue print.
After spending hours working with computer display, look at a blank piece of white paper, it would probably appear pink.
Babies are born with 300 bones, but adults have 206 bones.
It involves 17 muscles to smile & 43 muscles to frown.
Beards are the fastest growing hairs in the human body.
Every square inch of the human body has an average of 32 million bacteria on it.
Finger nails grow faster than toe nails.
Humans spend one-third of their life time in sleeping.
People do not get sick from cold weather; it is from being indoors a lot more.
The human brain stops growing at the age of 18.
The storage capacity of the human brain exceeds 4 tetrabytes.
Smart people have more zinc in their hair.
Our skin is the heaviest organ.
Our thumb equals with the length of our nose.
The teeth are the only part of the human body that can’t repair itself.
The average human body contain enough fat to make 7 bars of soap & enough phosphorus to make 2200 match heads.
The structural plan of a whale’s, a dog’s, a bird’s & a man’s arm are exactly the same.
In a square inch of the skin, lies 4 yards of nerve fibres, 1300 nerve cells,100 sweat glands, 3 million cells & 3 yards of blood vessels.
The average human blinks his eye 62,05,000 times a year.
15 million blood cells are destroyed in the human body every second.
The most sensitive cluster of nerves is at the base of spine.
Our skull is made up of 29 different bones.
A man who smokes a pack a day will loose 2 teeth every 10 years approximately.
Our hairs and nails are still growing even after our death.

S. SELVALAKSHMI
I Msc APPLIED PLANT SCIENCE

DO YOU KNOW?

• A crocodile cannot stick its tongue out.
• An ant can lift fifty times of its own weight.
• An ostrich’s eye is bigger than it’s brain.
• If you shout consistently 48 years, 7 months & 6 days, you will produce sound energy which can heat one cup of coffee.
• Elephants are the only animal that cannot jump.
• Education is the word with all vowels.
• A snail can sleep for three years.
  
  
  SALMAN JAVED SYED
  I MSc APPLIED PLANT SCIENCE.

HISTORY OF THE DEPARTMENT OF BOTANY

The University Botany Laboratory (UBL) was established in 1930 a small unit at the Agri-Horticultural Society’s Gardens on Cathedral Road. In 1933 the unit moved into its own Laboratory building constructed behind the Senate House at Chepauk. On elevation as the Centre of Advanced Study the department moved to the Centenary building of the University of Madras. In 1985, the department was shifted to the Guindy Campus, into a five-floor building. The department, besides the CAS-SAP status of the University Grants Commission received financial support through the UGC-COSIST and the DST-FIST programmes.

Prof. T. Ekambaram was the first Honorary Director of the Laboratory. He was a plant physiologist who had his training with Prof. F.F. Blackman. During Prof. T. Ekambaram’s short tenure as Director, three Master’s theses and few publications appeared.

In 1933, Prof. M.O.P. Iyengar took over as the first permanent Director. Prof. Iyengar had worked on algae with Prof. F.E. Fritsch in London and was a respected teacher and botanist. At the UBL, he established a school of research in algology, the first of its kind in the country. The work he initiated was broad based and covered limnological observations of fresh water, estuarine, and marine algae, besides systematics, morphology, life-histories and cytology of algae. These pioneering, work brought international acclaim to Prof. Iyengar and to the UBL. Especially noteworthy were the contributions of the group to our knowledge of green, red and blue-green algae and of diatoms. Prof. Iyengar was invited to contribute a Chapter on Chlorophyceae in the Manual of Phycology edited by Prof. Gilbert M. Smith published by Chronica Botanica. Contributions continued to flow from several students who had their training from Prof. Iyengar.

In 1944, there was a re-orientation of the work from algae to plant pathology and mycology with the appointment of Dr. T.S. Sadasivan to the Directorship of the UBL in succession to Prof. Iyengar on his retirement. To begin with, work was initiated on soil borne diseases of plants, especially Fusariose wilts of cotton and pigeon pea, and on the ecology of soil-borne fungal pathogens and their interactions with root systems of plants. Several other areas were taken up for study later and these included: physiology of fungi and the physiology of host-pathogen interactions, particularly in Fusariose wilts in plants; techniques of bioassay, especially of heavy metals using fungi, spectrochemical studies on uptake of ions by fungi and by plants, the role of vivotoxins and of fungal enzymes in diseases syndromes, and respiration and electrophoretic studies on plant tissues. For the first time in the country, a given disease such as Fusariose wilt of cotton plants was taken up for in-depth study from many angles; autecology and behaviour of the pathogen in soils, host-pathogen interactions and disease systems, pathogenesis, and the role of toxins and enzymes in wilt, and the basis of disease resistance. These studies were later on extended to understanding of other disease systems such as Pyricularia blast of paddy, and tikka of groundnut due to Cercospora. In every case, special attention was paid to elucidating the basis of resistance/susceptibility of cultivars to disease. The UBL gained recognition as the centre for plant pathology in the country and this was reflected in the invitation to Prof. Sadasivan to serve on the Editorial Board of the three- volume international treatise on Plant Pathology published by the Academic Press in 1959.

The first Doctoral thesis to be submitted from the UBL was in 1947 and was in the area of Plant Pathology by Prof. C.V, Subramanian. In recognition of the outstanding work done over the years at the UBL it was chosen by the University Grants Commission for elevation to the status of a Centre of Advanced Study in 1963. The UGC sanctioned a Chair in Mycology to which Prof. C.V. Subramanian was appointed in 1964. Additionally, the University created a Chair in Algology to which Dr. T.V. Desikachary was appointed in the same year. The UBL received generous assistance from the University Grants Commission, the UNESCO and the U.K. (Under Colombo Plan) by way grants and equipments.

Prof. Sadasivan retired in 1973 and was succeeded by Prof. C.V. Subramanian as Director. Prof. Subramanian relinquished the Directorship in 1976 to take up the Jawaharlal Nehru Fellowship awarded to him. He assumed again in July 1979. The Golden Jubilee of the department was celebrated in 1980 and an International Symposium was organized. He was the founder President of the Mycological Society of India. He also was a member of the University Grants Commission during 1979-82. Prof. C. V. Subramanian retired in 1985 and now resides in Chennai and is an active participant of the activities of the CAS in Botany. He recently inaugurated the Platinum Jubilee Celebration of the Botany Department and also the Asian Conference on “Emerging trends in Plant Microbial interaction held on December, 2005. He is a great source of inspiration and encouragement.


Prof. Mahadevan became Director and continued till his retirement in June 1998. Prof. Mahadevan strengthened the instrumentation facility of the Centre. During his time several sophisticated instruments were added to the facility which include: Transmission and scanning Electron Microscopes, high speed Centrifuges, recording spectrophotometers and spectrofluorimeter with computer terminals, Electroporator, PCR thermocyclers and research microscope with Phase contrast, dark field and fluorescent objectives. He introduced the Computer culture in the Centre and the administrative staffs were given training in handling Computers. Basically a Plant pathologist and biochemist, he was interested in the degradation of secondary metabolites especially the biochemical pathways. One of his important findings was to designate dissimilatory Plasmids that were involved in microbial degradation of aromatic compounds. His other interest included: forest ecology, bioremediation, gene sequencing and bioinformatics. He organized an International workshop in 1986 to mark the Centenary Celebration of the eminent algologist Prof. M.O.P. Iyengar which was followed by an International Symposium on Phycology in 1987. The Indian Botanical Society elected Prof. Mahadevan as its Secretary and the Annual Conference was held in 1988 at the CAS in Botany. He also organized the Asian Conference on Mycorrhiza and the Asian Mycological Conference. He conducted the International symposium on Phycology to celebrate the 75th Birth anniversary of Prof. T.V. Desikachary in 1994 and the International Conference on Plant Pathogenic Bacteria in 1996. The laboratory manual published with his student Dr. R. Sridhar is a popular book of research scholars. He was succeeded by Prof. D. Lalithakumari.

Prof. Lalithakumari concentrated to work on Plant disease management first with reference to chemical fungicides and pesticides and later on with biological control of plant diseases. She developed protocols for protoplast fusion techniques in fungi, especially for strain improvement. Bioremediation of xenobiotic compounds and Industrial effluents, molecular mechanism of fungicide resistance, forecasting fungicide resistance, extra chromosomal and gene involvement in which in fungicide resistance, characterization of mitochondrial of genomic DNA of plant pathogen, mechanism of degradation of textile mill dyes, heavy metal detoxification and degradation of hydrocarbons were the topics perused during her period. Prof. Lalithakumari conducted several training programmes and workshops for the benefit of not only researchers but also for rural women and farmers. She convened the National Symposium on Phycology in the New Millennium and also the Annual meeting of the Phytopathological Society. Prof. Lalithakumari was also the coordinator of the Indian herbal Science Programme and developed Agrotechniques for selected medicinal Plants. She revived the Dr. E.K. Janaki Ammal Herbal garden at Maduravoyal and trained students in the study of medicinal plants. She was President of the AMI (Madras Chapter) and Fellow of the Indian Academy of Agricultural Sciences. Prof. Lalithakumari was recipient of the Hari Om Ashram Award, The Best Women Scientist award and Tamil Nadu State award for Environment. Prof. Lalihakumari retired in 2003. She moved to British Guyana on a teaching assignment and now is a research scientist at Michigan State University.


Prof. N. Anand became the Director in 2003. He took his Ph.D. under the guidance of the eminent Phycologists of the country, Prof. T.V. Desikachary and was awarded the D.Sc., degree of the University of Madras in 2004. He concentrated on developing modern infrastructure in the Centre besides improving the academic ambience in the Centre. He also served as the Dean (Research) of the Univeristy of Madras. He worked the micro-algae especially on the taxonomy and biology of the blue-green algae (cyanobacteria). The Ministry of Environment and Forests designated him as the Coordinator of the All India Coordinated Project on Taxonomy of algae in 2003 which he continues. He organized several training programmes, national conferences and participated in the organization of the 150th year celebrations of the Univeristy of Madras. He was succeeded by Prof. R. Rengasamy on January 2008.

Prof. R. Rengasamy joined the Centre in 1976, joined the faculty and obtained his Ph.D in 1981 under the guidance of Prof. V. S. Sundaralilngam. He has been working on ultrastructure and usefulness marine algae. His areas of interest include: cultivation of marine algae, investigate the role of sea weeds in bioremediation and as source of bioproducts, biofuels from microalgae and molecular taxonomy of microalgae. He recently organized a National conference on algal Biodiversity and Biotechnology. Additional grants from UGC for strengthening the infrastructure is now being utilized effectively. Prof. Rengasamy has been establishing rapport with Industries through projects and recently visited Australia for a major collaboration for research on Biofuels from algae.
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The department also has Prof. K. Manibushan Rao D.Sc., Prof. K. Natarajan. Prof. B.P.R. Vittal and Dr. M.V. Viswanathan as Emeritus Professors. Prof. G. Kulandaivelu has recently joined as Sesquicentennial Emeritus Professor. Dr. K. Janardhanan has joined as UGC Emeritus Professor. The Centre has also Research Associates under the DST-Women Scientist Programme, Dr. Sivakami Sundari, Dr. Prema Paul and Ms. Meena.


The Centre has been concentrating on research in three major thrust areas namely, Algology, Mycology and Plant Pathology. Ph. D., programme is the strength of the Centre. There are also M. Phil and post-graduate teaching programmes, M.Sc., Applied Plant Science and M.Sc. Industrial Microbiology. The Centre has excellent basic facilities, sophisticated Instrumentation facility, Library facility, networking facility and field laboratory.

The motto of the Centre from the time of inception is research of excellence.



Prof. N. Anand., D. Sc

GLOBAL WARMING

GLOBAL WARMING

V. ASHOKKUMAR - RESEARCH SCHOLAR.




One of the most serious environmental problems today is that global warming, caused primarily by the heavy use of fossil fuels. To overcome these problems the photosynthetic microalgae are the potential candidates, for utilizing excessive amount of carbon-di-oxide. Because when cultivated these organisms are capable of fixing carbon-di-oxide to produce energy & chemical compounds upon exposure to sunlight. The derivation of energy from algal biomass is an attractive concept in that unlike fossil fuels. Since microalgae are called the scavengers of environment, because their biomass has more advantages than the fossil fuels viz… it is non explosive. Example – 150’C biodiesel compared to 64’C of petroleum diesel &also it is biodegradable, free from sulphur & it reduces the emission of carbon-mono-oxide & carbon-di-oxide. Among the microalgae, Botryococcus braunii is an unique microalgal strain having 86% of long chain hydrocarbon which is directly extractable to yield crude oil substitutes by both physical & chemical process. However, the economics of fuel production from microalgal biomass is largely dependent on a microalgal carbon-di-oxide fixation step to that required for the production of biodiesel.