A major approach to learning about the way cells work is to study the chemicals of the cell. The shape and workings of molecules, that is, the complex chemicals, can be studied with a technique called X-ray crystallography. That approach involves first transforming the chemical of interest into crystals — a form in which there is a regular, stable pattern of atoms. Table salt and sugar are crystalline forms of simple chemicals, and are easy to prepare. But more complex chemicals and structures can be challenging to crystallize. Once crystals are made, their structure is revealed by bombarding them with X-rays. The X-rays are deflected by individual atoms, and the pattern of the deflected rays, collected on X-ray film, or by other methods, is studied in order to infer the atomic architecture of the molecules.

In 1953 when the structure of DNA was solved, it was in part due to the work of another Jewish woman scientist, Rosalind Franklin, who in the 1940s and ’50s, used X-ray crystallography to study DNA crystals and concluded that DNA was a twisted helical molecule. Unfortunately, she did not live long enough to be awarded a Nobel Prize for her ground-breaking work on that monumental problem; she died of cancer at the age of 38. James Watson, Francis Crick, and Maurice Wilkins received the Nobel Prize in medicine or physiology for DNA structure in 1962.

X-ray crystallography of ribosomes has helped to reveal how they work to produce proteins, which build and control everything that living organisms do. But ribosomes are made up of extremely complex combinations of various chemicals, including a variety of proteins and RNA (a chemical cousin of DNA). Scientists who first attempted to study ribosomes could not crystallize them. “Ribosomes deteriorate fairly quickly,” explained Ada Yonath in an interview with Adam Smith of the Nobel Foundation. As a young scientist working in the 1970s, she was frustrated by failed attempts to form crystals for analysis. “At one point I had to describe what I was doing…. [I]t was like climbing Mount Everest, only to find out there was another mountain behind it.”

Ironically, her breakthrough in research came when she had a bicycle accident and suffered a severe concussion. “I had some free time and had to recover. I read a lot,” said Yonath. Through her reading she learned that polar bears from the North Pole had ribosomes that were special; the bears needed a way to preserve their ribosomes over the severe winter and had evolved a way to pack them on membranes to protect them. “Maybe this can be used to solve the structure of the ribosome,” she thought. That was when she came up with the idea of studying ribosomes from very hardy species. “I used ribosomes from very, very robust bacteria,” said Yonath.

X-ray structures of the two ribosomal subunits from bacteria.

The most robust bacteria are those that live at extreme conditions, such as bacteria that live in very hot or in very salty conditions. Yonath ended up studying thermophilic bacteria from hot springs, as well as bacterial species native to Israel that live in the Dead Sea. The hardy cells turned out to have resilient ribosomes, which enabled her to form the useful crystals. Over the last three decades, Yonath’s work, along with that of Thomas Steitz, Venkatraman Ramakrishnan, and their co-workers, has aimed to refine the procedure, and in the process learn how ribosomes work in greater detail.

Further breakthroughs credited to these scientists have shown that antibiotic drugs that bind to ribosomes can block their function and kill cells. Since bacterial cells have ribosomes that are different from animal cells, it is possible to develop drugs that can target disease-causing bacteria and help people recover from serious illnesses. “The ribosome is very important,” Yonath explained. “It is a target for many antibiotics.… We want to increase the possibility of the antibiotic to distinguish between the patient, who has to recover, and the pathogen, that has to die.”

Dr. Edward Friedland, an orthopedic surgeon from Wyckoff, commented on Yonath’s scientific breakthroughs. “What she has gotten recognition for is a wonderful advance in many regards. It may allow us to find ways to break down resistance of many bacteria to antibiotics,” he said. One of the major problems in medical practice today is the development of antibiotic resistant strains of bacteria that spread from patient to patient in hospitals and other medical facilities. “If we could get into the mechanisms of the ribosomes, we could get over the resistance,” said Friedland, who serves on the New Jersey regional board of the American Committee for the Weizmann Institute of Science. Friedland visited Weizmann Institute last November and “was impressed with its scope and the number of different aspects of science that they’re involved in.”

“They are exploring multiple facets of science on a basic level,” he noted. “Methicillin Resistant Staph Aureus — you can’t fight them. Thousands die because of resistant bacteria. Her research is outstanding and opens the door to future research.”