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Chair of Reproductive Biology, Director Scottish Centre for Regenerative Medicine, University of Edinburgh; Author, After Dolly
Biologist; Cloning Researcher; Roslin Institute, Edinburgh; Coauthor, The Second Creation

Research in Biology and Medicine Will Provide the First Effective Treatments for Many Diseases

I am optimistic that during this new century research in biology and medicine will provide the first effective treatments for many diseases, although we cannot predict when they will become available and in some cases it may take several decades.

A greater number of new treatments may well be developed than was introduced during the twentieth century. I make this judgment not only on the basis of a simple extrapolation from developments in the past, but also on a consideration of the new understanding that is being established at present and of the revolutionary techniques that are emerging. Consider as examples the potential value of the genome mapping projects, stem cells and the techniques to assess many thousand small molecules for their ability to have desired effects upon human cells in laboratory test systems. All of this is underpinned by rapidly advancing molecular biology providing essential understanding of the mechanisms that regulate cell function.

Entirely new opportunities are being provided by the mapping of the genomes of people, other mammals and a variety of infectious agents that cause human diseases such as malaria. Although we now know the entire genetic sequence of a small number of people and have new estimates of the number of genes in the human genome, we have a great deal to learn about the role of specific gene products and the mechanisms that ensure appropriate functioning of the genes. Those actively involved in this aspect of research believe that this stage in the development of human genetics will be far more demanding and take far longer than the mere mechanical reading of the sequence. However, it will in the end be very rewarding.

It has been appreciated for sometime that some human diseases result directly from differences in DNA sequence, but despite considerable research efforts only a small number of causative mutations have been identified. Modern, rapid sequencing techniques will greatly facilitate these analyses in the future. However, it is likely that in a far greater number of cases sequence differences make people comparatively vulnerable to disease, but are not directly causative of that disease. These associations will only be revealed by large-scale studies in which the genomes of hundreds, perhaps thousands, of people are determined while also monitoring the incidence of diseases in that population. This may make it possible to provide accurate warnings to people that they are vulnerable to specific diseases, while also offering advice on life style and medication to reduce that risk.

In time information of this kind may also greatly increase the accuracy of selection of appropriate medication for particular patients. At present an adverse response to medicines is a major cause of death or the need for hospital treatment, even if the medicine is appropriately prescribed and taken. This is because of differences between people in the response to drugs. It is probably fanciful to think of tailoring medications for each person, because this implies a full knowledge for every person of their likely response to and metabolism of every compound that might be considered as a medicine. However, it does seem likely that understanding of these mechanisms will lead to improved design and selection of new compounds.

A great deal has been made of the potential use of stem cells or their derivatives to replace those lost in degenerative diseases that reflect the death or malfunctioning of specific cell populations. Diseases that are considered suitable for treatment in this way include Parkinson’s disease and other neurodegenerative diseases, juvenile diabetes, spinal cord injury, liver damage resulting from hepatitis or solvent abuse. In their haste to consider this use of stem cells, the potential benefit of using such cells for drug discovery and toxicology studies is overlooked. Drug assessment will be markedly more accurate as cells become available that are representative of the critical tissues of a variety of different people.

In some cases, the cells will be genetically identical to those of patients with an overt inherited condition. There are a number of potential sources of such cells, but at present the most likely seem to be embryo stem cells because they are known to have two key characteristics. They have the ability to form all of the different tissues of an adult and they are able to multiply almost indefinitely in the laboratory. In practice this means that researchers will have the opportunity to study genetically identical cell populations again and again over a period of years and to examine their response to potential drugs. 

This is not known to be the case for any cells taken from adults. The gene sequence known to be associated with a specific disease may be introduced into existing cell lines to create a population of cells that would be expected to exhibit the characteristics of the disease. Alternatively, it may be possible to use somatic cell nuclear transfer from a patient with an inherited disease to obtain embryo stem cell lines having that characteristic even if the causative mutation is not known.

In some cases similar research may be provide an understanding of the molecular mechanisms that regulate the function of stem cells in a tissue. In time, this may make it possible to stimulate the replacement of damaged or lost cells from endogenous stem cell populations in the patient. There would be many practical advantages in being able to use this drug-based approach to cell therapy. The alternative will be to produce cells of the required type from embryo stem cells, in sufficient number that they can replace the lost cells. When they have reached the appropriate stage of their maturation these must then be inserted into the damaged tissues in such a way that they are able to integrate fully into that tissue and restore normal function. While it is likely that each approach to cell therapy will be used for some diseases, there are clearly many potential benefits to a drug based therapy.

I am optimistic that research has the potential to provide these new opportunities, and many more not described. However, I am concerned that society tends to be frightened by innovations while taking for granted the treatments that are available. We would make the most rapid progress if we recognized that it was earlier research that led to the present treatments and if we were excited by the challenges and opportunities that will arise from new research.