A time to meet new and difficult challenges

Bob Williamson calls on long experience to express hopes for the future.

I often comment on how lucky I am to have lived from BC ('before cloning') to AD ('after Dolly'). Because so many people in medical research are young, they do not easily identify an important change that occurred about 20 years ago.

When I started in 1960, we made and labelled our own ATP in the lab, made our own enzymes, and even collected fractions by hand, sitting in the cold room. Technological innovations, such as PCR and transgenesis and the internet, and the availability of reagents and machines mean that technology is no longer limiting. In a very short space of time, we have moved from being ideas-rich but techniques-poor, to a point where technology is in the hands of anyone with a generous NIH grant or a start-up company. If you have an idea, try it out. It will probably only take a few weeks, cost a few bucks, and be available for computer modelling.

Perhaps because of the availability of ever more powerful reagents and equipment, we seem to live at a time where ideas are scarce. This is compounded by advice to young scientists to jump through the hoops (and establish a good track record in one thing, rather than move around). Indeed, fewer grants are going to young scientists, and in Australia we see the growth of 'be sure to do it before you submit the grant, and don't be adventurous, or you won't be funded'. What a pity!

Where will the advances be in coming years? All progress today occurs in interdisciplinary areas, not in the silos. Two great areas of human biology are still almost untouched.

One is the brain, and in particular human 'intelligence', which distinguishes us from all other species on earth. The other is that period in human development between fertilisation and about six weeks, when differentiation occurs and our tissues are laid down. These are also the times and place when most of the genes we don't understand, fully two-thirds of human genes, are expressed.

Understanding brain structure and function

I would predict that the most dramatic increase over the coming decades will take place in our understanding of brain structure and function. The advances will come from women and men who can put together knowledge in four fields: the human genome (because that is where it starts), imaging (especially MRI), neurology (to understand what goes right by what goes wrong), and artificial intelligence (to model with computers what we learn).

Why does a child with an extra normal copy of chromosome 21 differ from us in some ways ('executive function') but not in his ability to play music or draw? How plastic is the brain, and for how long?

Stem cell research is the most promising approach to applying this knowledge in medicine. We can already predict many aspects of health and disease for an individual, based on gene data. You may be at risk of cancer, I may be at risk of heart disease, he may have asthma and she may have endometriosis. Knowledge is all very well, but we need approaches that allow us to modify risk and improve health. Such interventions must be safe and long term.

Gene therapy, alas, has proven to be more difficult than we predicted. Our defences against taking up exogenous genes from other species and allowing them to function in our bodies are very strong. When genes have been introduced using viruses, the outcomes have often had a high element of risk, so only the most severe disorders are candidates for treatment.

Cell therapy

In contrast, I have been very impressed by approaches that use cells for therapy. Autologous cells from a patient appear to help in conditions like heart attacks. I look forward to the time when they can also be used to treat cystic fibrosis and Friedreich ataxia and muscular dystrophy.

Diseases affecting children should, in theory, be easier to treat using cells, as those affected are young, provided the cells can be genetically corrected. To do this, we need to develop nuclear transfer to generate pluripotent cells from individuals that have 'better function' but will not be rejected by the immune system. Alas, our country is almost on its own in making nuclear transfer illegal, because of the fiction that such transfer is 'cloning' that gives an 'embryo', when it is nothing of the kind.

Participating in public discourse

The last and related hope for the coming decade is that scientists raise their level of participation in public discourse. Medical research is essentially ethical and positive; it is a contract between the patient, the scientist and the community to make things better for those who have a medical problem. It empowers patients, families and the community, because knowledge is power. In future, every scientist must be an advocate for research. We have to prove to people that we believe in the value of our research, in its ability to help to make this a better country and world.

Prof Robert Williamson, AO, FRS, FAA is now at 'The Dean's Ganglion', Faculty of Medicine, The University of Melbourne, having recently retired as Director of the Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne. He can be contacted at r.williamson@unimelb.edu.au.