An important discovery

"Gene therapy strategies will come in with a major cost advantage since DNA interference technology will act at the DNA level at lower doses, reduce toxicity and only one or two copies of the DNA"

- Dr Ramanand Nadig 
President Operations and  
Deputy Dean 
Clinical Research Education and Management Academy (CREMA)

Genes are segments of DNA present in the chromosomes in the nucleus of every cell. Genes carry instructions for making proteins, which are then copied by special enzymes into many copies of messenger RNA (mRNA). The mRNA then comes out of the nucleus, into the body of the cell; where it goes on to create the proteins needed for everyday life. Faulty or mutated genes lead to malfunctioning proteins that cause disease. Gene expression can be blocked by restricting the ability of chromosomal DNA to be copied into RNA and made into proteins. This research has given the lead wherein the ways to correct genetic disease by changing mutant gene sequences to its normal has been made possible.

Cancer patients will be the prime beneficiaries of gene silencing. Dr Rohit Joshi, Medical Oncology, Assistant Professor, Department of Medicine, Christian Medical College, Ludhiana, says, "The process of gene silencing is important for the differentiation of many different types of cells. Gene silencing or Ribonucleic Acid Interference (RNAi) has been described as one of the major science breakthroughs. It is a revolutionary technology, but it has many limitations. The exaggerated hope is that it will cure everything. Most of the research in this field has been in botany, with major potential seen in human research. Every few months a newer and better way to do something is revealed, but it is every few years that something of real worth is discovered or invented. Gene silencing is meant to fit into the latter category." He adds, "The prospects for this technology in developing therapeutic applications for diseases including cancers, autoimmune dysfunctions and viral infections are enormous. Additionally, it can be used as a tool for determining gene function. If you can selectively switch off a gene, you can then observe its biological function."

Controversy's child

Safety and quality issues have always dogged the vaccine sector, and when the National Regulatory Authority was recently de-recognised by the World Health Organisation, it took down the reputation of domestic vaccine players with it. Aashruti Kak reviews past and present vaccine controversies

Since the inception of vaccination in the late 18th century, there have always been concerns over the morality, ethics, effectiveness, or safety of vaccination. However, the general medical belief has been that the benefits of preventing various diseases, and therefore, death from infectious diseases offset the risks of adverse effects following immunisation. This reasoning is justified, as prevention is always better than cure. Vaccines have proved to be a much more cost-effective strategy to promote and protect health compared to treatments of acute and chronic diseases. In fact, vaccines have saved more lives than all the 'wonder drugs' put together.

It is only in the 1990s that vaccines started to attract controversies because of certain rumours about various side-effects, that they may cause, including auto immune disorders, autism and so on. Safety will always be a primary concern, but it is normally understood that all vaccines may cause side-effects. One such controversy that has managed to stay alive till date is the presence of thiomersal (International Nonproprietary Names—INN), commonly known as thimerosal, in vaccines. This is a mercury containing antifungal widely used as a preservative to prevent life threatening microbial contamination. Although US Food and Drug Administration (USFDA) has found no evidence of harm from the use of thimerosal as a vaccine preservative, other than local hypersensitivity reactions, there is a theoretical possibility of thimerosal being neurotoxic. However, with frequent modifications in manufacturing technology, the need to add preservatives during manufacturing has gone down.

There are still many companies that use the preservatives in their drugs and biologicals. Dr Suresh Jadhav, Executive Director, Serum Institute of India Limited (SIIL), says, "Some of our vaccines and those of other companies available in the market do still contain thimerosal as a preservative. There is a clear Position Paper of WHO, and now even the Centre for Disease Control and Prevention (CDC) of USA, that acknowledges the fact that thimerosal has not been found to be responsible for any of the adverse events or neurotoxicity, which has been caused following the use of vaccines containing the organomercurial." He adds, "There is a clear guidance as per WHO that a vaccine that is distributed in multi-dose containers must contain preservatives. However, some vaccines which are available in mono dose/single dose containers are preferred without preservatives." SIIL is currently working on meningococcal A conjugate vaccine, measles aerosol vaccine, rotavirus vaccine and seasonal pandemic influenza vaccine.

In today’s safety conscious world, it becomes imperative for companies and governments to be extra cautious to earn the trust of the population they are serving, otherwise incidents like the measles vaccine deaths in Tamil Nadu (April 2008) and Aurangabad (September 2008) cannot be controlled or curbed. It becomes even more important during an outbreak of a disease, where one of the most vital steps in ensuring protection is to monitor vaccine safety, because during an emergency, more vaccines are given, which could lead to more adverse events; more rare and serious adverse events may occur because people of all ages and health conditions would be vaccinated; and most importantly, the usual testing of a vaccine before its widespread use may be shortened to speed up its availability.

"In case of an epidemic/outbreak, to the best of my knowledge the Indian Government has a system in place. They have various laboratories under their control such as National Institute of Communicable Diseases (NICD), National Institute of Virology (NIV), National Aids Research Institute (NARI), and several laboratories working under Indian Council of Medical Research (ICMR)," says Jadhav. He continues to say that with respect to the benefits of vaccination, if a vaccine is already available against the outbreak/disease, then it can be used in the population in and around the centre of outbreak. "There is no question of using a vaccine, which is 'hurriedly' tested. All the vaccines need to be fully tested by the manufacturing laboratories, and then, are also to be tested/released by the National Control Laboratory; only then the product can be actually distributed and used. In view of this, the question of causing more adverse events using hurriedly tested vaccine does not arise," he adds.

In the US, it has the the Vaccine Adverse Event Reporting System (VAERS), a national vaccine safety surveillance programme co-sponsored by the FDA and the Centers for Disease Control and Prevention (CDC), that detects and analyses possible adverse events that occur after the administration of US licensed vaccines so scientists can find out if it is the vaccine that is causing health problems.

Regulatory compliance issues in India

As of today, there are five Indian vaccine manufacturers who are pre-qualified by WHO for supplies to UN agencies, says Jadhav. These manufacturers, in addition to catering to the Indian requirements, both in the private market as well as government programmes, also meet 65 to 70 percent requirement of UN agencies for Bacillus Calmette-Guérin (BCG), tetanus toxoid (TT), diphtheria and tetanus toxoid (DT), diphtheria, tetanus and pertussis (DTP), measles, rubella, measles and rubella (MR), measles, mumps and rubella (MMR), polio, rabies, hepatitis-B and haemophilus influenza type-B vaccines. "In fact, one of the UN Millennium Development Goals was to reduce mortality due to measles by 50 percent in Africa by 2010 as against what was in 1997. In reality, this has been achieved much earlier ie before November 2007, and that too not only 50 percent.

Mesenchymal stem cells might be the answer to spinal cord injury  
In India, 20,000 new cases of spinal cord injury are added to the list every year, as compared to 11,000 in US and 700 in UK. Stempeutics Research has done a pilot study on the application of mesenchymal stem cells in spinal cord injury. Patients with fresh injuries have responded well to this therapy. Although many cell types contribute to organ repair in spinal cord injury, bone marrow mesenchymal stem cells have the greatest potential for repairing the spinal cord injury. Stempeutics has collaborated with Manipal Hospital for these pilot studies.