Recipient's Response

by Ada Yonath
Winner of the 2008 Albert Einstein World Award of Science

(Princeton University, November 11, 2008)
I would like to express my appreciation for this exceptionally prestigious award in sciences. I feel deeply honored and extremely grateful. Receiving the 2008 Albert Einstein World Award of Science has a special meaning for me, as undoubtedly Albert Einstein is a superb model to follow! His creativity, originality and accomplishments have inspired me and played a special role in my studies. Even as a high school student I was stimulated by his concepts and originality. Hence I chose the Special Relative Theory as my Physics Project.

Winning prizes was very far from the motivation for initiating the studies that eventually brought me here. I was dreaming about revealing the mechanisms underlying a fundamental life process, protein biosynthesis, in which the ribosomes that exist in each living cell (which can reach 6.000.000), are the key players. These complex cellular assemblies comprising over 50 components function as efficient nano-machines with extremely low mistake rates and constantly translate the genetic code into proteins, the molecules responsible for almost all life processes in all living cells.

Ribosomes have been investigated comprehensively by biochemical methods in several leading research institutes and universities since the middle of the last century. When I initiated my studies, over two decades ago, it was clear that detailed understanding of the mechanisms underlying ribosome function hinges on structural information. Furthermore, as owing to its vital role in life, the ribosome is a target for many antibiotics, it became evident that revealing the ribosome structure should lead to discoveries concerning the mode of the inhibitory action of antibiotics. My dream was to understand how the small antibiotics can paralyze ribosome functions, how resistance to antibiotics can be acquired, and how the antibiotics distinguish between the pathogenic bacteria and the mammalian patients. I have no word to express my current feelings, when not only can we answer these questions, but we can also provide structural tools for the design of more advanced antibiotics.

At that time, the feasibility of the determination of the accurate three-dimensional structure of the ribosome met with considerable skepticism from most of the international scientific community. The only method yielding molecular structures is X-ray crystallographies, which require high-quality crystals. However, ribosomal properties are unfavorable for crystallization: they are flexible, heterogeneous and unstable. Repeated failures of leading scientists when attempting to crystallize ribosomes led to the common conception that ribosomes cannot crystallize, and consequently to the overwhelming doubt in the fruitfulness of ribosomal crystallography.

You may wonder: why did I believe in the ability to reach this goal. Here I should be thankful for the North Pole bears that hibernate in winter. As ribosomes in living bodies disintegrate within a few days, most of the ribosomes of the hibernating bears should vanish during the winter. While hibernating, the bears require limited metabolism and therefore need only a very small number of ribosomes, but once the winter is over, the bears must immediately start active life; hence they need a large pool of ribosomes. If hardly any ribosomes remain intact in the bears’ body throughout the winter, how can it come back to life in the spring?

A study which revealed that, within the cells of hibernating polar bears, the ribosomes are packed periodically on their membranes, in arrangements similar to monolayer crystals, provided the idea that pushed me onwards. I assumed that this packing is the means nature takes to limit ribosome disintegration and maintain ribosome functional activity. Therefore I concluded that ribosomes possess properties that should be favorable for crystallization. Hence, my strategy was to mimic the bears!

In collaboration with the late Prof. Wittmann, the Director of the Max Planck Institute for Molecular Genetics in Berlin, I have undertaken this challenge. We identified robust bacterial sources, expecting that their ribosomes would disintegrate more slowly. For maintaining the active conformation long enough for crystallization, procedures developed at the Weizmann Institute by Zamir, Miskin and Elson, were employed. To our surprise and satisfaction, micro crystals diffracting to high resolution were obtained within a few months already in 1980!

However, even when we obtained larger crystals, about six years later, pursuing the crystallographic end met with enormous hurdles. For instance, once we irradiated the crystals by X-rays, they deteriorated immediately. All biological materials are sensitive to X-rays, including crystals of proteins and other cell components, but in most cases measurements from their crystals are still possible. However, the ribosomal crystals are exceptionally sensitive. Can you imagine, ladies and gentlemen, spending years in order to obtain a crystal, and then watching it vanish within a faction of a second? We reasoned that the fast decay of the ribosome crystals is due to their loose packing, which allows rapid propagation of free radicals that are formed by the X-radiation. Therefore we aimed at slowing their progression by introducing the method called cryo crystallography, which overcame this terrible situation and became routine worldwide almost instantaneously.

This was not our last problem. Unpredictable as well as foreseen difficulties kept appearing. Thus, every day had its problems but at the same time, almost every day had its rewards. For me and my group, every step forward was a little victory. We felt as if we were putting together an enormous puzzle. However, every time we thought that I had reached the highest mountain, we kept realizing that a higher peak was still in front of us. With all of these colossal obstacles on our way, recognition at the level of prizes seemed far and totally unrealistic. In fact, now I am wondering, how would my scientific life proceed if my sole incentive was winning prizes? Surely not the way it went. I would certainly pick a simpler and more “doable” project….

Before ending, I would like to use this opportunity to thank the distinguished committee who selected me as a recipient of this prestigious prize and by expressing my deep and sincere gratitude. Furthermore, with your permission, I would like to cite one of the greatest scientists, Isaac Newton. He believed that almost everyone can reach heights in their work if they focus on a single endeavor to the exclusion of all else. Newton claimed no more for himself than the ability to concentrate. Apparently, he could afford it. In our days how can people focus when they face so many distractions? When, for mere survival, all scientists must report frequently and display their successes?

Some of you may know that my scientific history is somewhat different from what is considered to be the “usual path”. For a long time, I was allowed to focus on ribosome crystallography, and was tolerated as long as I demonstrated some progress towards reaching my ultimate goal.
Thanks are due:

- to the members of my research group for their devotion and enthusiasm in good and, more often, in bad times;

- to the Weizmann Institute for supplying a permanent home for me despite my intensive collaboration with the Max Planck Society, which supported this project from its early stage and established an independent research unit for Ribosomal Structure;

- to Ms. Helen Kimmel for establishing the Kimmelman Center for Macromolecular assembly, which promoted structural biology at the Weizmann Institute to heights not known previously;

- to the United States National Institute of Health (NIH) who financed my dream from its embryonic stage, despite the severe doubt expressed by most (but, obviously, not all) of the scientific community worldwide; and continues to do so even after several prominent US groups stepped into this field;

- to the various synchrotron radiation facilities, who provided the sophisticated means for our experiments, although for a long period these seemed to be rather unproductive;

- to my family, who supported me throughout with no questions or complaints, although my mind was not always solely given to them. This includes my parents, who were brought up far away from science; especially my mother, who experienced enormous difficulties in raising and educating me after my father’s death, when I was still a child; my sister, Nurit; my daughter, Hagith, who had to tolerate me in my presence and my absence; and my granddaughter, Noa, who at the age of 5 invited me to her kindergarten class, in order to explain how ribosome works.