Stem cell research offers great hope for treating previously incurable diseases, says Oliver Brüstle, if only governments will allow it to be undertaken
Stem cell technology has sparked huge controversy. On the one hand is the hope that embryonic stem cells can be used to generate cells to replace those damaged by diseases such as Parkinson’s, diabetes and heart failure. Embryonic stem cells are the only stem cells that can generate all the cells of the body, be expanded indefinitely and be subject to single-gene modification. On the other hand there is fear that by deriving stem cells from fertilized eggs we are interfering with human life.
Ground-breaking discoveries are bound to raise fears. Stem cell technology raises fundamental questions: When does life begin? Is it acceptable to use spare fertilized eggs – that is early human embryos – to derive cell lines? Is it, on the other hand, acceptable to discard thousands of frozen eggs each year, thus hindering the development of new cures? And, finally, can our laws meet this challenge or do we have to redefine the onset of human life?
Three ways of tackling innovation
One approach to innovation in stem cell technology is to see it as a national opportunity, as in Britain. With landmark developments such as Dolly, the first cloned sheep, Britain quickly sorted out ethical and legal issues. The legal framework was designed to accommodate the technology in the most flexible yet responsible manner, and with an eye to attracting frustrated scientists from more restrictive countries.
The second approach is much more more cautious, as in America. The US government has promoted tough restrictions for federally funded research to keep conservatives happy but has kept its hands off the private sector.
The third approach is to linger and first contemplate all risks – a route taken by German lawmakers. Since technological risk assessment can never be complete, this strategy is a recipe for paralysis. In Germany, work is restricted to embryonic stem cell lines isolated abroad before January 2002; establishing new cell lines in Germany can result in a three-year prison sentence. This approach could isolate German researchers from the mainstream.
Stem cells and therapies
Although adult stem cells derived from blood and bone marrow have been used for many years to treat blood disorders such as leukaemia, structural repair of non-regenerative tissues such as brain, heart and insulin-producing cells has remained a challenge. Here, embryonic stem cells with their capacity to generate all tissues and cell types of the body could serve as unlimited donor source for neurons, cardiomyocytes (heart muscle cells), insulin-producing cells, but also liver cells, bone, cartilage, blood vessel and blood cells, skin and many others. These “artificially” derived cells could be used to repair damaged areas in organs such as the brain and spinal cord, heart, liver and pancreas. The first targets for cell replacement will be diseases associated with local cell damage: Parkinson’s disease and Huntington’s chorea (diseases of the nervous system), myocardial infarction (heart disease), diabetes, liver damage and the like. But stem cell technology is neither about growing organs in a dish nor a miracle worker: cures for cancer and ageing will remain in the lab for some time.
In addition to classic cell replacement, embryonic stem cells have the makings of savvy Trojan horses. Today’s technology allows modification, inactivation or replacement of almost any gene in embryonic stem cells. This makes them ideal vehicles for introducing missing enzymes into diseased tissues. Tailored to individual patients’ needs and equipped with sophisticated genetic remote control systems, these cells could eventually be used to target inflammatory, immune and metabolic diseases, and also neurological disorders such as epilepsy, pain and depression.
Before stem cell products sell as therapies, they will hit the market as tools for drug development. The initial phase will be to exploit the large variety of embryonic stem cell derivatives for drug-screening purposes. For the first time it will be possible to study pharmacological and toxicological effects of compounds in largely unaltered human neurons, cardiomyocytes, liver cells and the like – prepared under standardized conditions in virtually unlimited quantities. These strategies are bound to outperform 20th-century screening methods based on highly artificial cell lines and animal experiments.
The second phase will exploit the amenability of embryonic stem cells to genetic modification. Genetic engineering will permit the introduction of candidate mutations for a large panel of diseases, and these cells will serve as cellular models for the development of new therapies. “Alzheimer neurons” from the laboratory dish might be used to study directly the molecular machinery underlying the disease process and to screen and develop compounds in association with the target cell – an approach that could revolutionize drug development.
A telescope on the body
For biologists, stem cells are akin to the astronomer’s telescope, permitting them to peek into the very origins of tissues and organs. The development of the nervous system, heart muscle and many other tissues can be studied live under the microscope. The implications are enormous. It will become possible to explore the role of individual genes in human tissue development, pin down factors that might be responsible for malfunction and identify mechanisms that make a cell adopt another identity.
An international code of conduct
Stem cell research is about to revolutionize both biomedicine and our conception of life. We need an international code of conduct. Although reproductive cloning and modification of an individual’s genome have to remain off limits, a blanket ban on stem cell research is not a viable option.
It is essential to distinguish between research that ought, urgently, to be banned, and research that might merely interfere with particular national legislations. Missionary attempts to expand over-restrictive national regulations into worldwide conventions typically fail to receive sufficient support and, in the end, delay international bans where they are really needed.
An international code is also essential for scientific collaboration and for the protection of intellectual property. The development of stem cell-based medicines and therapies does not fall within the realm of academic research but requires an array of competitive biotech companies developing drugs and treatments.
These enterprises will only thrive in environments that offer sufficient patent protection to encourage investment. The current reluctance of the European patent office to grant patents that relate to stem cell technology will further promote the exodus of scientists and biotech companies to more permissive jurisdictions.
Oliver Brüstle is a professor in the Institute of Reconstructive Neurology at the University of Bonn, Germany.