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RNA Quest May Unlock Cell's Street

NOW that J. D. Watson and company have outlined their construction manual for DNA (deoxribonucleic acid), the carrier of genetic information for all cells, many scientists agree that the best target for further research is RNA (ribonucleic acid). The cell copies specific genetic instructions from the DNA into RNA and then transports the RNA from the nucleus to the cytolpasm. It has not yet been determined how the cell chooses which information to copy and how the RNA is transmitted.

Fotis C. Kafatos, assistant professor of Biology and popular lecturer in Biology 15b, has spent the last two years investigating the cellular and molecular aspects of cell differentiation (how the cell decides what role it will play). Kafatos, a 28-year-old Greek citizen, has already published a dozen scientific communications which have received international attention. The editors of Nature cited his scientific promise and the crucial nature of his work in a rare burst of praise in the May, 1967, issue. Born in Crete, he came to America immediately after high school and enrolled at Cornell University. He finished the four year program in three years, graduating first in a class of 100 with high honors in Zoology.

He took his Ph.D. degree at Harvard with Carroll Williams, professor of Biology. When asked about Kafatos, Williams said "Fotis is in a group by himself. I've never seen anyone with such a green thumb for identifying the critical phenomenon and devising the necessary experiment." Williams relates how one of his colleagues, after watching Kafatos present his findings, said "God may be dead but Zeus isn't." Williams used to be one of the heads of the developmental biology course Kafatos now teaches with John G. Torrey, professor of Botany. But "Kafatos is such an enchanting and lovable teacher that I soon realized he could do the job as well as I could, so I resigned," Williams said.

Escaping the Cocoon

KAFATOS' FIRST major research project at Harvard, performed while a graduate student, was an investigation of how a moth escapes from its cocoon. The Elementary Science Study program has published an account of the way he found "How a Moth Escapes from its Cocoon." It will be used in elementary schools in September. In the pamphlet's preface, Kafatos states that science courses should not teach only the well-ordered results of research but also the daily progress of research, but also the daily progress of research, including the disappointments as well as the illuminations. He claims this would encourages frustrated beginners and would present a realistic picture of scientific work.

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The answers Kafatos found in this project eventually presented him with a tailor-made system in which to pursue his old interest in cell differentiation. Through other scientists' research he found that different species of moths had various means of escaping from their cocoons. He found that, for example, one Australian species has a hard, pointed structure at the front of its head that it uses as a saw and that the caterpillar of one kind of silk moth leaves an exit hole when it builds the cocoon. The species Kafatos chose to work with, the Chinese Oak Silk Moth, however, had no such obvious method.

He soon found that the moth opens its cocoon by wetting it with some kind of liquid that softens the glue holding the silk threads together. Kafatos discovered that a certain drug made the liquid appear on the moths' face, even when they were not trying to escape from a cocoon, and collected the liquid efficiently by applying the drug. After realizing that the liquid must contain some material in addition to salt and water, Kafatos guessed that an enzyme, a chemical agent that helps break down or "digest" other chemicals, was the liquid's active element.

At first he believed the liquid was produced in the moth's digestive system. Analysis of the moth's digestive apparatus showed that there was a large amount of protein-digesting enzyme present but it was not certain this was the same enzyme as in the liquid. To confirm that the enzymes were the same, Kafatos became a bug surgeon, removing the midgut of twenty moths. As expected, none of the moths produced any liquid. Yet he was not satisfied with the result: it seemed too easy. He later realized that the pupae he used had been refrigerated for some time to prevent them from developing into moths at the usual time. Months later, as a safeguard, he repeated his surgery on twenty young, healthy moths. They were able to produce the liquid. At that point Kafatos still had no idea where the active element was synthesized.

The First Drop

WHILE dissecting pupae in search of the liquid's production site, he noticed a pair of long, very thin tubes in the front part of the pupa. These were the remains of the silk-producing tubes of the caterpillar. They led to a single opening on the moth's face just underneath the mouth. It was impossible to tell exactly where the liquid comes from since the first drop appears suddenly and covers the face. Yet the mouth and the old silk tubes were the only two openings and the mouth could be discounted because Kafatos had already shown that the enzyme came from nowhere in the digestive system.

He plugged up the silk tubes with melted wax, leaving the mouth open. When the liquid-producing drug was administered, no liquid appeared until the wax was removed. Kafatos was certain that the liquid did come from the tubes. Yet when he mashed the tubes, expecting to find the enzyme, no enzyme was present. One of Kafatos' typical brainstorms saved the day. He realized that the liquid he had been collecting was produced by two glands. The old silk tubes produced the inert part of the liquid while a special gland on the face secreted the enzyme itself. Kafatos substantiated these findings by proving that the moths could produce the enzyme even if the silk tubes were removed at an early stage of the pupa's development.

He soon noticed that there was some white, crystal-like powder on the face of a moth that was ready to emerge from its cocoon. Most of the enzyme crystals were on two cone-shaped structures on the face, called maxillae, which scientists had hither-to believed useless to the silk moth. Kafatos also found concentrated enzyme solution in the maxillae's cells, which squeeze the solution out through fine tubes leading to the surface of the maxillae. The enzyme, mixed with the liquid of the old silk tubes, gets painted over the cocoon's tip, thus dissolving the cocoon's glue and enabling the moth to push the strands apart and escape.

The Cellular Level

Puzzled by the changing function of the moth's old silk tubes and fascinated by the process which commits cells to their various fates, Kafatos turned to developmental biology on the cellular level. He presents his own findings in this field in two lectures in his course. He often involves his undergraduates, as well as his graduate students, in his projects. Kafatos is investigating both how cells become specialized and how they sometimes change from one specific function to another. These questions are crucial for man's understanding of the cell's nature. Furthermore, since cancerous cells are previously normal ones which, for some reason, begin to change and spread wildly, his research may eventually prove to be valuable in the fight against cancer.

THE Cell Theory, formulated in 1839, states that all living matter is composed of cells, which are made up of nuclei and cytoplasm. In the last two decades scientists have found that DNA, a long double--chained molecule found in the nucleus, carries the cell's genetic information. This information is the blueprint that describes how the working parts of the cell, the proteins, should be assembled from 20 building blocks, the amino acids. Thus DNA ultimately determines the cell's function. The DNA's information is transferred to RNA (the cell's working manual), which is chemically like DNA except that it is usually single-stranded. Specific RNA messages ("messenger RNA") are shipped to the cytoplasm and there direct synthesis of the specific proteins.

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