The Hindu Business Line : Stem cell research in India

Given the huge disease burden and the need for organs, affordable diagnostics and therapies, the promise that stem cells offer needs to be exploited to the fullest.

EVER since the race to map the human genome began in the 1990s, the excitement in modern biology has been rising. Work in the areas of genomics, proteomics and now stem cells, holds the promise of revolutionary developments in medicine and an enhanced understanding of life on earth.

As scientists started tinkering with the genes, unravelling the mystery behind the role of each gene, issues of ethics (cloning of humans) and social problems cropped up. In diagnostics, new treatment methods, drugs and equipment to delve deep into modern biology, corporates saw opportunities to rake in billions of dollars.

Amid the hype and hope that these areas of biology offered, there have been a fair number of scientific claims that are questionable and short-cut methods that have come a cropper. The recent, and most shocking, is the case of the South Korean scientist Hwang Wu Sook, whose headline-grabbing work on cloning, published in Science and Nature in 2004 and 2005, unravelled as a case of scientific fraud. Hwang had claimed to have cloned an adult dog, a big first, in August 2005.

In cloning research, Dr Ian Wilmut and his team at the Roslin Institute in Scotland made the first breakthrough with `Dolly', the sheep, in 1997. It was followed quickly by Polly, another sheep, and then came ANDi, the rhesus monkey, a couple of years later. Thereafter, steady progress in cloning has been reported.

In the present instance, the investigative panel at Seoul National University found that most of the precious human embryonic stem cell colonies that Hwang Wu and his scientists had claimed to have used were fakes. The colonies were said to have been derived from embryos that were clones of 11 patients, marking the first alleged proof that it might be practical to create custom-designed stem cells to treat disease.

Embryonic stem cells, which have the potential to become — and perhaps repair — virtually every kind of affected organ, have been made before, but never from cloned embryos. Scientists believe that clone-derived cells are less likely to be rejected by a patient's immune system. Stem cells have the ability to continuously divide and transform into various types of tissues.

As of now, the three broad applications of stem cells are:

They provide deeper insights into embryonic development;

They can be magic bullets to cure such debilitating diseases as Parkinson's, Alzheimer's or diabetes; and

They can aid pharma companies in early stage screening of drugs, thus cutting on costs and bringing life-saving drugs to the market faster.

If Hwang's results were false, then after seven years of attempts worldwide, no one has succeeded in getting `therapeutic cloning' to work on a practical scale, said scientists closely involved in stem cell research.

What do all these developments mean for India? Where is stem cell research heading in our country? The Indian National Science Academy (INSA), the leading body of scientists, said strict guidelines need to be put in place to put stem cell research on a strong footing.

Given the huge disease burden, the need for organs, affordable diagnostics and medicines, the promise that stem cells offer needs to be exploited to the fullest. However, there are pitfalls, in the form of false claims, unethical methods to get quick results or unregulated practices to harvest these `miracle' cells. As Dr C. M. Habibullah, a liver specialist who has done considerable work in using foetal stem cells collaborating with the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, cautions, some private companies have started setting up facilities for cell banks, and some doctors are claiming miracle cures for diseases such as muscular dystrophy. This trend needs to be brought under check.

There is also keen interest from big biotech companies in the US, Canada and the UK, in joint venture projects with Indian researchers.

Dr Habibullah says umbilical cords and foetal cells are good sources for stem cells. For example, in Andhra Pradesh alone, 23 lakh deliveries take place every year in hospitals. Similarly, at least 10,000 medically terminated pregnancies are reported, which can be a source for foetal cells.

The Indian Council for Medical Research allows the use of foetal cells up to 14 weeks of pregnancy. The big question, however, is how will these cells be put to use a few years down the line, and how well will the stem cell banks that are coming up maintain them, in the absence of specific guidelines.

Ironically, the draft guidelines prepared by the ICMR and the Department of Biotechnology a couple of years ago have remained just that. They need to be translated into legislation, says Dr R. A. Mashelkar, President of INSA and Director-General, Council of Scientific Research (CSIR).

Dr Lalji Singh, Director, CCMB, whose lab has a majoron-going programme on stem cells, concurs. Dr Lalji is for allowing of therapeutic cloning research in the country, as it could find cures to many diseases. Interestingly, while the spare embryos created during the In Vitro Fertilisation (IVF) process can be used for research using embryonic stem cells, the unregulated proliferation of IVF clinics is worrying.

The CCMB has a collaboration arrangement with the Deccan Medical College (DMC) for liver stem cell research. The DMC and the Japanese Nichi-in Centre for Regenerative Medicine, which has developed a gel that preserves stem cells, are ready to undertake human trials using stem cells in end-stage liver failure patients.

The CCMB has also done work with the L.V. Prasad Eye Institute in growing corneal limbal cells, which help in repairing the damaged corneal tissue and restoring vision. Doctors have successfully performed more than 200 such procedures.

The CCMB is working with Biological E on the use of cord blood cells and is venturing into newer areas. It has simultaneously built up facilities that can aid industry and other research institutes. For example, its Nuclear Magnetic Resonance (NMR) imaging facility being set up with the help of the Department of Science and Technology (DST), would allow imaging of cells and enable an insight into the effects of drug molecules at the cellular level. This would obviate the need to sacrifice animals for scientific experiments. It has also developed transgenic gene models of mice, for conducting drug trials. Overall, research efforts by the scientific community or industry are still at modest levels, though a few major groups are working in specific areas. As early as 2001, Reliance Life Sciences and National Centre for Biological Sciences, Pune, had built up facilities to preserve seven and three stem cell lines respectively.

The All-India Institute for Medical Sciences (AIIMS) has claimed reasonable progress in therapeutic stem cell research work. Using bone marrow mononuclear cells, it has initiated clinical trials on about 40 patients. The focus is on treating muscular dystrophy, spinal cord injury, cerebral dysplasia, heart tissue damage, diabetes and motor neuron disease.

Even as scientists and lay persons alike remain divided on the hype, hope and ethical issues surrounding stem cells and cloning, countries have evolved their own policies, ranging from permissive to restrictive. For example, the US and Germany have restrictive policies on stem cell research and funding owing to ethical issues. In contrast, the UK, Singapore, Japan, South Korea, Belgium and Israel are more liberal. Taking the middle ground are countries such as Australia, Canada and Spain. To protect its own interests, India needs to urgently put in place a carefully-thought-out policy in this area.