WHAT'S TO BLAMEFOR MULTIPLE SCLEROSIS?

By David N. LeffScience Editor

Counting noses _ 15,000 of them _ is how Canadianresearchers have solved the nagging puzzle of whethermultiple sclerosis is an inherited disease, or caused byenvironmental factors.

Answering this question is trickier than it looks, and sowas the method they employed. It's described in today'sissue of Nature under the title: "A genetic basis forfamilial aggregation in multiple sclerosis."

For openers, molecular geneticist G.C. Ebers at theUniversity of Western Ontario, in London, Ontario, withhis associates in the Canadian Collaborative StudyGroup, surveyed 15,000 people with multiple sclerosis.They came from 14 regionally based multiple sclerosisclinics across Canada.

Each patient completed a detailed questionnaire detailinghis or her family relationship. This data enabled Ebersand his colleagues to compare the occurrence of multiplesclerosis in the offspring of biological parents with thosewho had been adopted.

"Studies of adopted children," Ebers wrote, "require largepopulations . . . . They have been used with success inbehavioral disorders, to discriminate between genes andenvironment, but have not been reported in autoimmunedisorders [such as multiple sclerosis]."

The prevalence of multiple sclerosis "in northernEuropeans living in high-risk areas such as Canada,"Ebers noted, amounts to 0.1 percent _ one in 1,000people. But in first-degree relatives it rises to 3 or 4percent, and among identical twins reaches 30 percent.

Multi-Thousand Population Census Provided Answers

These familial statistics strongly suggest, but do notclinch, an inherited basis for multiple sclerosis. It took thenationwide, multi-thousand population census to do that.

The 238 adopted multiple sclerosis patients in the entirecohort studied were adoptees who had lived with their470 non-biological parents since infancy. They had 345adoptive siblings and 388 children. All told, these 1,201non-biological family members numbered among themonly a single multiple sclerosis patient, (an adoptingparent), thus neatly matching the one-in-a-thousandprevalence in the general population.

In other words, despite a lifetime of shared familyenvironmental circumstances, 1,200 parents, siblings andoffspring failed to develop the multiple sclerosis incurredby their 238 non-biological adoptees as they grew up.

On the other hand, 34 of those 238 were able to report on46 of their biological parents, who had given them up foradoption. Of these, four individuals _ 9 percent _ hadbeen affected with multiple sclerosis. Ebers observed thatthis rate was "substantially greater than the populationprevalence, but comparable to those with first-degreebiological relatives."

That group contrasted with 815 non-adopted multiplesclerosis cases, of whose 5,055 biological parents,brothers, sisters and children, 92 _ 5.5 percent _ hadthe disease.

"The observation that the prevalence of multiple sclerosisamong non-biological [adopted], first-degree relatives ofmultiple sclerosis index cases," Ebers concluded,"challenges the notion of a transmissible agent or anyfamilial microenvironmental factor." He interprets thisfinding "to indicate that familial aggregation in multiplesclerosis is genetically determined; . . . no effect of sharedenvironment was detectable"

He suggested that "if these findings were to provegeneralizable to other autoimmune disorders, they mayserve to divert the search away from specific uncommonviruses . . . ."

One Commentator Takes Exception

New York University pathologist Byron Waksman entersa demurrer: In an editorial comment to Ebers' Naturepaper, Waksman _ a retired research director of the U.S.National Multiple Sclerosis Society _ observed: ". . .although Ebers and co-workers were unable to detect anyeffect attributable to shared environment, things may notbe quite so simple."

Shared environment, said Waksman, "undoubtedly doesplay a part in the induction of disease among biologicalrelatives who live with the index [multiple sclerosis]case, and who are susceptible to multiple sclerosis."

Waksman added that "The factors responsible forinducing multiple sclerosis . . . must be strictlydistinguished from the factors that trigger relapses [orexacerbation] of this disease once it has been induced.Here upper respiratory and gastrointestinal virusinfections appear to play a key part . . . ." n

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