Biography – Dr. Ehud Shapiro

Function Professor of Computer Science and , Weizmann Institute of Science,

Education & Professional Born in Jerusalem in 1955, Ehud Shapiro was awarded a B.A./B.Sc. Background degree with distinction in Mathematics and Philosophy from in 1979, and a Ph.D. in Computer Science from Yale Univer- sity in 1982. His doctoral studies with Prof. attempted to provide an algorithmic interpretation to the noted philosopher of science 's approach to scientific discovery. Joining the Weizmann Institute’s Department of Computer Science and Applied Mathematics in 1982 as a postdoctoral fellow, Prof. Shapiro was inspired by the Japanese Fifth Generation Computer Systems project to invent a high- level for parallel and distributed computer sys- tems, named Concurrent .

In 1993, Prof. Shapiro took a leave of absence from the Weizmann Institute to found and serve as CEO of Ubique Ltd., an Israeli Internet pioneer. Prof. Shapiro returned to the Weizmann Institute in August 1998, where he is now an associate professor in the Depart- ments of Computer Science and Applied Mathematics, and Biological Chemistry, and incumbent of the Harry Weinrebe Chair of Computer Science and Biology.

Preparing for his return to academia, Prof. Shapiro ventured into study of . Initially curious about the origins of life, he was sidetracked into attempting to build a computer from biological mole- cules, guided by a vision of "A Doctor in a ": a biomolecular com- puter that operates inside the living body, programmed with medical knowledge to diagnose diseases and produce the requisite drugs.

Prof. Shapiro is currently leading research projects at the interface of computer science and molecular biology at the Weizmann Institute of Science. His group designed a tiny computer made entirely of biologi- cal molecules which was successfully programmed – in a test tube – to identify molecular changes in the body that indicate the presence of certain .

2

The computer was then able to diagnose the specific type of , and to react by producing a drug molecule that interfered with the can- cer cells’ activities, causing them to self-destruct. For this work Shapiro received the 2004 World Technology Network Award in Biotechnology and was a member of the 2004 "Scientific American 50" as Research Leader in Nanotechnology.

In other projects, Prof. Shapiro designed an effective method of synthe- sizing error-free DNA molecules from error-prone building blocks and developed a biological model that may explain the root cause of genetic disorders that include the Huntington disease. He has also developed a method for tracing the “genealogy” of cells in the human body, an ap- proach that in being used to investigate fundamental questions in biolo- gy and medicine, recently providing the most conclusive evidence to date that cancer originates from a single cell of a mature organism.

Abstract The cell lineage tree of a person captures the history of the person’s cells since conception. In computer science terms it is a rooted, labelled binary tree, where the root represents the primary fertilized egg, leaves represent extant cells, internal nodes represent past cell divisions, and vertex labels record cell types. It has approximately 100 trillion leaves and 100 trillion branches (100,000 bigger than the Human ); it is unknown. We should strive to know it, as many central questions in biology and medicine are actually specific questions about the Human cell lineage tree, in health and disease: Which cancer cells initiate relapse after chemotherapy? Which cancer cells can metastasize? Do insulin-producing beta cells renew in healthy adults? Do eggs renew in adult females? Which cells renew in healthy and in unhealthy adult brain? Knowing the Human cell lineage tree would answer all these questions and more.

Fortunately, our cell lineage tree is implicitly encoded in our cells’ via mutations that accumulate when body cells divide. Theo- retically, it could be reconstructed with high precision by sequencing every cell in our body, at a prohibitive cost. Practically, analyzing only highly-mutable fragments of the genome is sufficient for cell lineage reconstruction. Our lab has developed a proof-of-concept multidiscipli- nary method and system for cell lineage analysis from somatic muta- tions. The talk will describe the system and results obtained with it so far, and a proposal for a FET Flagship project for uncovering the Hu- man cell lineage tree in health and disease.

Tecan Trading Ltd., Seestrasse 103, CH-8708 Männedorf, Switzerland T +41 44 922 81 11, F +41 44 922 81 12, [email protected], www.tecan.com