WHAT’S the difference between Stuart Little and William Shakespeare? Answer (to a very rough approximation): about 300 genes.
This week sees the official unveiling of the entire genome of the lab mouse, or at least a first draft of it. One feature of this genetic blueprint seems certain to hog the limelight: just how similar it is to our own (see “Of mice and men”). The crucial difference is you can experiment on mice in ways that would be wholly unethical and impractical with humans.
Want to know what a particular human gene does to, say, brain or fat cells? When or where it switches on during development? What happens when it is disabled, or made to work overtime? Go to Mus musculus and manipulate the equivalent gene. This is what makes the mouse genome so crucial to the future of biological research, and for fully understanding our own genome.
Advertisement
The implications for tackling human disease, however, are rather less clear-cut. The mouse genome will certainly speed up efforts to trace genes and proteins linked to disease, and lead to many more mouse models for disease. But this is no guarantee of progress in the clinic. The identities of the defective genes that cause cystic fibrosis and Huntington’s have been known for years, yet we cannot correct these defects with drugs. And look at variant CJD: we know that abnormal proteins cause it, but don’t yet have a drug that can stop these agents doing their worst.
In time, genome research will surely deliver many new targets for drugs: genes and proteins whose very existence, let alone function, was previously obscured. But finding potential targets is seldom the hard part of drug research. It’s developing compounds that actually work against such targets, and in people rather than just lab mice, that is costly and slow. Malaria researchers have no shortage of candidate molecules, or antigens, for vaccines. What they lack is the knowledge and know-how required to assemble these antigens into a vaccine that stimulates a long and lasting immune response. There is even a danger that drugs researchers will become bogged down by the sheer volume of genetic information now coming their way.
Much of this may be obvious but is easy to forget amid the headlines and hype that tend to accompany genome announcements. It’s easy to forget, too, that while the mouse genome itself was bankrolled by governments and charities and is freely available to all, many of the discoveries flowing from it will not be. The mouse genome will spark the creation of vast numbers of genetically modified mice. Those of commercial value are likely to end up patented. And some companies and labs will inevitably seek broad patents that could impede research.
Remember the OncoMouse? This was a lab creature engineered in the 1980s to develop tumours mimicking those in human cancers. Though based on one specific cancer-causing gene, the company controlling the rights to the mouse won a patent giving it ownership over the whole idea of genetically engineering an animal to be prone to cancer. Even now, years later, anyone who creates such an animal, no matter what genes or species are involved, risks having to pay the company royalties or at least seek its permission to continue with their research. The mouse genome could unleash a plague of similar patents unless governments, medical charities and scientific institutions start challenging them in the courts – or better still, prevent them being awarded in the first place.
Geneticists are also going to have to tread carefully over animal welfare. Mouse experiments might not provoke quite the passionate opposition triggered by those involving cats, dogs or primates, but as the range of mouse mutants grows, researchers can expect increasing scrutiny from welfare campaigners. At the top of the campaigners’ hit list will be mutations that appear to produce suffering with little clear pay-off.
Such thoughts may irritate researchers who are keen to make progress, but they cannot be ignored. It is often said that the mouse will be to mammalian biology what the fruit fly is to invertebrate science – the key to discovering how a linear DNA code produces staggeringly complex three-dimensional creatures. In the end, though, a mouse is not a fly. It is a mammal with a genome not dissimilar to our own. That is why it is valuable to science. It is also why science must treat it with respect.