key: cord-015023-ishxfinx
authors: Jones, David
title: Hard water
date: 1995
journal: Nature
DOI: 10.1038/377106a0
sha: 
doc_id: 15023
cord_uid: ishxfinx

nan

the index case, and who are susceptible to MS.

Data obtained in an earlier study by Ebers' group, which looked at sibpairs in MS families, supported a role for genes and for shared exposure to environmental agent(s) in determining the age and year of onset of MS in the members of each pair 2 • The incomplete penetrance of susceptibility genes in identical twin pairs also points to the importance of environmental influences in the occurrence of disease among those with the appropriate genes.

Ebers and his colleagues express the hope that their findings "may ... divert the search for environmental clues away from specific uncommon viruses to a broader category of events occurring early in life which are applicable to regional populations"; this comment is presumably aimed at Kurtzke and those sharing his view 3 that existing epidemiological data point to a specific infectious (presumably viral) agent as a direct cause of MS. No such agent has ever been successfully linked to MS, however, either by direct isolation or by indirect (for example, serological) means, despite claims for some twenty different viruses. The epidemiological data 4 fit equally well with a model of disease induction in genetically susceptible individuals by common viruses and mediation by a secondary process, such as autoimmunization against myelin or other brain antigens.

The situation in MS is reminiscent of that in poliomyelitis, in which there is a clear relation between the age at which viral transmission occurs and the age at which attack by the virus on the central nervous system commences. The incidence of neurological disease increases in individuals of higher socioeconomic status within a population (because this tends to be associated with viral transmission delayed to late childhood or early adolescence) and in populations living at temperate latitudes (these, in general, enjoy a better standard of living, again with later transmission of common childhood infections). A similar requirement in MS for late viral transmission has been demonstrated in a well controlled, populationbased study that showed an almost tenfold increase in the risk of contracting MS as the age (up to puberty) of infection with common childhood viruses (such as measles) increased 5 • The ability of viruses to cause autoimmunization is not in doubt. It was shown over a decade ago 6 that measles in humans occasionally results in T-cell sensitization against myelin basic protein (MBP) and this sensitization is associated with an inflammatory demyelinating 'postinfectious' encephalomyelitis. The same relationship has been demonstrated in rats and mice infected with suitable strains of coronavirus or measles virus 7 • 8 • Such 106 cross-immunization is usually attributed to molecular mimicry 9 • A recent report establishes that T-lymphocyte clones from MS patients specific for a single encephalitogenic MBP peptide recognize configurationally similar peptides of several common viruses equally well 10. These cells are stimulated by either viral or MBP peptides to proliferate and secrete inflammatory cytokines.

The factors responsible for inducing MS, the thrust of Ebers and co-workers' contribution, must be strictly distinguished from the factors that trigger relapses (or exacerbation) of this disease once it has been induced. Here upper respiratory and gastrointestinal virus infections appear to play a key part, as first reported by Sibley et al. 11 and dramatically confirmed more recently by Panitch 12 • The interval before relapse, however, is measured in days or weeks, whereas initiation of the process that leads to MS may span a period of years -Kurtzke, in his Faeroe Island studies, calculated an average interval of six years 3 • Also, although new T lymphocytes with pathogenic potential may be generated at each relapse, other factors may predominate, such as systemic release of inflammatory cytokines like 'Y-interferon, as part of the viral infection. This would result in upregulation of the MHC on vascular and glial elements in the central nervous system, which in turn would allow new lesion formation. Administration of 'Y-interferon in quiescent MS patients does in fact provoke symptoms of the disease, which correlate with MHC expression on circulating monocytes 13 • Time will tell whether other (non-infectious) agents also play a role in inducing MS. The infectious/autoimmunity hypothesis has proved remarkably fruitful, but other influences, such as climate, general levels of infection and neuroendocrine processes call for deeper investigation. D 

Hard water ENGINEERING materials must not only be strong: they must be stiff as well. Indeed, stiffness is often more important than strength. Plastics, for example, are excluded from many engineering uses not because they would break, but because they would bend.

In this connection Daedalus recalls that the stiffness of a tube can be increased by pumping a fluid through it. At a critical flow rate it even becomes infinitely stiff. Any deflection is then perfectly opposed by the internal flow.

Increase the flow further, and 'negative stiffness' sets in -the pipe will react against a load. At higher flows still, oscillations occur. This is what makes a fire hose wriggle under a fast flow. DREADCO's engineers are now exploiting these facts. Aircraft and rockets, for example, have to be very light but stiff structures; they also depend on liquid fuels pumped at high velocities. The DREADCO workers hope to achieve the first requirement with the aid of the second. Many aircraft already store their fuel in compartments in their wings, and little modification should be needed to pump it to the engines through the hollow spars of the wing structure.

Indeed, this trick has already been proposed for supersonic aircraft to allow the flowing fuel to absorb frictional heat from the leading edges.

A light and flimsy aircraft or rocket, stiffened in flight by its flowing fuel, should be supremely efficient. More cunning still, its stiffness and damping could even be altered in flight by redistributing the fuel flow between different spars of the structure. The various flutters and instabilities which plague aerodynamics could be played off against each other, shifted away from dangerous resonances, or otherwise made harmless. The computing power already built into all modern aircraft and rockets could implement such strategies in real time with great aplomb.

Another application is more earthbound. Daedalus is designing a large, light building with a structural frame of plastic piping. This will be stiffened by pumping water continuously through it. Some of the water will be used by the normal domestic and heating or cooling requirements; the rest will be recirculated. The idea is to withstand earthquakes. A severe shock to the structure will stop the pumps. The building will then lose, not its strength, but its stiffness. It will absorb the battering in a flexible, rubbery manner, neither falling down nor injuring the occupants. When the danger is past, it can be pumped back to normal structural rigidity.

David Jones NATURE · VOL 377 · 14 SEPTEMBER 1995

Trends in European Multiple Sclerosis Research