Interview with Nobel Laureate Rolf Zinkernagel.
Dr. Rolf M. Zinkernagel, along with Dr. Peter C. Doherty, was awarded the Nobel Prize for Medicine in 1996 for his discovery relating to the "specificity of the cell-mediated immune defence". They discovered, on the basis of their work done at the John Curtin School of Medical Research (Australian National University, Canberra), how the immune system recognises virus-infected cells. This laid the foundation for an understanding of the mechanisms used by the cell immune system to recognise foreign micro-organisms as also its own molecules.
The discovery revolutionised clinical medicine as it helped strengthen the immune response against invading organisms and cancers, apart from diminishing the effects of auto-immune reactions in inflammatory conditions such as rheumatic situations, multiple sclerosis and diabetes. This opened up a whole new area of research in vaccine development.
A specialist in immunology, Zinkernagel (57) is Professor at the Institute of Experimental Immunology, Department of Pathology, University of Zurich, Switzerland. Since 1981, his work has won him at least one award every year from reputed international institutions.
Zinkernagel was in Chennai recently to deliver a lecture at an International Immunology Conference. In an interview to Asha Krishnakumar, he explained the progress of immunology research and its clinical implications. Excerpts:
What major areas of immunology research have benefited the common man?
There are three major areas. One is vaccines and vaccinology. All the important vaccines that work today were developed in the last 50 years.
Second, certain complications arise where there is incompatibility between the blood groups of a set of parents; it has to do with the "rhesus antibody" that closes the red blood cells of the baby. Immunology studies have shown that the mother's influence on the baby can be treated so that this complication does not arise.
The third area which has developed over the last 10 years or so is the production of highly specific antibodies using the monoclonal antibody technique. These can treat some forms of leukaemia, help fight infections, work against certain rheumatoid diseases and so on.
What is the current focus of immunology research?
It is difficult to pinpoint any one area. But many people are working on vaccines, not only against HIV, tuberculosis, leprosy and so on, but against a whole lot of diseases which are of major concern, particularly in the Western countries, such as cancer. Another focus is on ways to prevent auto-immune diseases such as diabetes.
Does immunology vary with sex, age, ethnicity, environment, genes and so on?
From studies on populations in the West we know that the incidence of auto-immune diseases in females is about five times that in males. This clearly shows that sex can make a huge difference with regard to immune-mediated diseases. That probably has something to do with the importance of the mother in transferring her antibodies to the foetus and/or the baby - through her blood or milk.
Age is an important factor. We know that there is no immune activity at birth. It takes 6 to 12 months for the immune system to develop. The immune system matures and functions best around puberty - 12 to 15 years. From then on it declines very slowly. Around 60-65 years, the immune system is at a very low ebb. At that time diseases such as tuberculosis may recur because the immune-surveillance has gone down.
There is some evidence, not strong as yet, that immunology varies with ethnic groups. Take for example the rapid increase of diabetes in India. It sort of looks like an ethnic difference. In the U.S., there are differences in the incidence of diabetes between Afro-Americans and whites. Yet it is not conclusive. More research is needed.
The difference in immunology between countries and the environment is related mostly to hygiene status and the use of vaccines. Environment makes a huge difference to immune systems. For instance, it is clear from Indian data that nutritional status plays an important role in the development of the immune system. This is also borne out by data from some Western civilisations. Tuberculosis and so on are rampant among the undernourished population. There are other indications that vitamins and certain metals such as zinc play a major role in the development of the immune system. Thus poverty is certainly a factor that hinders immune system development.
There are huge differences in the immune system with respect to genetic factors. This is because the immune system, particularly cell-mediated defence, has something to do with the transmission of HL-A (histocompatibility lymphocyte A system) antigens. HL-A antigens vary from person to person. These molecules, which are expressed on the cell surface, have a direct influence on immune reactivity. So there is a strong and direct evidence of genetic influence on immune systems. But there are other factors, such as interferon and so on, that sort of balance out genetic differences.
Will the human genome project give a boost to immunology research? What possible new directions can it take?
The human genome project as well as the projects on animal genome will certainly have a major impact on biology, including immunology. The genome projects give us something like the index of an encyclopaedia. That is, we now know what is in the genome. But we do not have the explanations as yet. Whenever we find anything new in any form of experimentation, we can now go to the encyclopaedia, find out from the index and then fill in the details on what it means. In very general terms, the genome projects will benefit the understanding of immunology a lot.
What is the future of research in immunology and the treatment of immune-mediated diseases?
Immunology as a system deals mostly with acute infectious diseases that tend to kill the host. This is true of animals and humans. We have learnt that most of these diseases are readily taken care of either by vaccines - polio, measles and so on - or by antibiotics. The immune system is not really developed for many other things, such as against tumours and slow-onset and chronic diseases such as hepatitis C. These are very slow onset diseases. So people survive for 10 to 30 years from the time they get these infections and the disease process does not interfere with procreation.
So the future of immunology is in understanding these slower types, such as tuberculosis, leprosy and HIV, against which we have no vaccines. There are many diseases that eventually become debilitating but which cannot be controlled except through antibiotics, particularly tuberculosis and leprosy. It would be much cheaper and efficient if we had a vaccine against them.
This is true of tumours as well. The immune system is very inefficient against tumours. So it is important to devise clever methods to use immunity against tumours.What are you working on now?
I am working on these chronic types of infections. I try to understand what we need to do to improve immunity against them and tumours. Tumours are also like chronic infections, slowly progressing over 5 to 20 years. You only see them in the final stages. So it is a very similar problem.
I am also trying to understand why our immunity against our own proteins sometimes ends up in auto-immune diseases. It is a similar slow process that we do not understand.