Light cast on a darkling gene - retinoblastoma

Michaelle Vancek, a charming, cheerful, and clever girl of three, has the dark, Indian- tinctured beauty of her mother, an Ecuadorian immigrant. But as nurses ready her for the ophthalmology operating room at New York Hospital in Manhattan, she no longer seems charming or especially pretty. She screeches and wails. She yells ''ugly lady'' at one of the nurses. Clutch- ing the remnant of a pajama top that's her security blanket, she writhes and kicks so ferociously that two people must hold her down for the anaesthesiologist to slip a gas mask over her face.

''It's better when they carry on like this,'' says Robert Ellsworth, the chief ophthalmologist. ''It isn't pleasant for the parents, or for our eardrums, but the kids go out faster because they take deep breaths of the gas.''

After a few moments, Michaelle's screams have faded into the slow, thick breathing of unconsciousness. The ophthalmology team quickly gets to work. Ellsworth clamps Michaelle's right eye open with a lid speculum and begins probing around the perimeter of her eyeball with a pen-sized scleral indentor. Peering through his ophthalmoscope, he looks at the retina, the innermost sensory area of the eye, where light is translated into nerve impulses. Michaelle is a victim of retinoblastoma, a potentially lethal eye cancer, and Ellsworth, who has treated more cases of the malignancy than he can count, is checking for fresh tumor growth.

''Holy God, look at this!'' he cries. ''Look in there.'' In a mirror attached to the side of the ophthalmoscope, the tumor appears as a white, foamy mass in the pupil. Magnified some eight times, it looks immense, although it's smaller than a pinhead. ''See the way it just lifts up into the eye?'' says Ellsworth. ''Just like a dish of vanilla ice cream with whipped cream, eh?'' He pokes around with his indentor. ''That tumor is calcified,'' he concludes triumphantly. ''If there were any living tumor left, it would have a translucent sheen, like fish flesh. We treated it with radiation, and now it's dead. And because it isn't on the area of central vision, this eye will see twenty-twenty, even though ninety-five per cent of the retina has been destroyed.''

Michaelle's left eye is another matter. It's artificial. Even radiation couldn't destroy the massive tumor in it, and late in 1985 Ellsworth removed the entire eyeball. ''That was terrible, terrible, when the doctor told us the eye had to come out,'' says Michaelle's father, John, a building superintendent in midtown Manhattan. ''Now we look at her and think how much more beautiful she would be with both eyes. We just pray that one day we have good news, so that other

children with the disease can be treated without removing the eye.''

Retinoblastoma is as rare as it is tragic. It occurs in only oneof 20,000 births, and only af- flicts children under the age of four -- some of them newborns. Being treated for it is a harrowing experience. Although burning with a laser or freezing can occasionally cure a tumor, more often the victims of retinoblastoma must endure either powerful blasts of whole-beam gamma radia- tion, which can impair the growth of the skull, or have an eye ''enucleated'' -- a euphe mism for removed. In Western nations, where the malignancy is usually caught early, the ''cure'' rate exceeds 92 per cent. But in poor countries, ret inoblastoma is nearly always fatal. Even when it's treated successfully, survivors aren't necessarily home free. Children like Michaelle, who have the hereditary form of the disease, may develop in adolescence a second, genetically related bone cancer called osteosarcoma. And they have a fifty- fifty chance of passing the ret inoblastoma trait on to their children.

Yet John Vancek's prayers for future retinoblastoma suf- ferers -- perhaps his own grand- children -- may soon be answered. A recent and spec- tacular discovery by scien- tists at the Massachusetts Eye and Ear Infirmary in Boston and the Whitehead Institute for Biomedical Research in

Cambridge, Mass. has buoyed hopes that retinoblastoma may become the first human cancer to be fully understood at the source of all malignancies: in the genes. As the vicors in a scientific race under way at least since 1980 in half a dozen laboratories, Thaddeus Dryja, Stephen Friend, and Robert Weinberg have isolated and cloned the gene believed to govern retinoblastoma and os- teosarcoma -- a gene that induces cancer not by its presence, as is the case with all other cancer genes found to date, but by its absence or its inability to function. This has led some researchers to call it the first anti-cancer gene.

In the field of cancer biology, where hype, gee-whiz ardry, and proclamations of the Answer to Cancer are all too familiar, doctors and researchers have hailed the work of Dryja, Friend, and Wein- berg as a genuine break- through. Even competitors in the retinoblastoma race have joined in the praise. ''I tip my hat to these guys,'' says Webster Cavenee, director of the Montreal branch of the Ludwig Institute for Cancer Research. ''We're accustomed to studying animals as a way of understanding human cancer, and we're always struggling to extend observations in mice up to humans. But this discovery needs no qualifiers. It's the first gene of its kind we've found that we know is clearly involved in human cancer. No ifs, ands, or buts about it.'' Says Ray White, a molecular biologist at the University of Utah who has studied retinoblasto ma since 1981, ''The implications of finding the gene are just enormous. It's the next obvious step in understanding the genetics of cancer.''