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n his eyes, a chemical reaction, the way one molecule changes when it encounters another, carries with it a bit of ancient magic, a kind of modern translation of the alchemist's art. Alchemists searched for the philosopher's stone, the elixir that would turn base metals into gold. Sorensen, an assistant professor of chemistry at TSRI, and head of his own small laboratory in The Skaggs Institute for Chemical Biology and the Department of Chemistry, is after gold of another kind.

Sorensen is searching for what may be one of the most elusive substances on the face of the earth -- the useful molecule.

"The reason we love novel chemical reactions so much," Sorensen says, "is because we can make use of these reactions. We can take these molecules, these commonplace building blocks that don't really have a utility, and transform them into molecules that are truly useful. There's a basic biomedical relevance to everything we do here."

There is also a subtle, yet pronounced, beauty hidden beneath all that relevance. Sorensen, who received his appointment to TSRI just three years ago, refers to it as architecture, an intrinsic part of the molecular landscape where he does his work. In real life, he explains, the craftsman's constructions are made visible, the stone wings of a gothic cathedral, the glass skin of a van der Rohe skyscraper. In chemistry, the architecture is the molecule itself, and the beauty of the design is the potential effect that molecule will have on patients.

"The fruit is the molecule that comes out of the synthesis," he says. "Hopefully, it's something of benefit. Alchemists were the first chemists but they had no idea what they were doing. We like to think we know what we're doing now."

For Sorensen, organic chemistry presents itself as a paradox, what he calls "an unusual science." Organic chemistry thrives on empirical evidence and rigorous experimentation, yet its capacity to predict reactions and solutions is highly impressive. If, for example, you take molecule A and molecule B, and set out to combine them at the chemical level, there is a very good chance that Sorensen and his colleagues can predict your chances of achieving this new synthesis with a high degree of accuracy. In many cases, they can predict what the chemical outcome of the combination will be, what it will do and how it will work.

But sometimes molecules surprise you. They do something different than you ever thought possible. In those moments, it's not hard to imagine Sorensen and his colleagues standing around like their ancient counter-parts, gaping at the magic transpiring before them.

REASONING BY ANALOGY

"To a large degree, chemistry is still an empirical science," Sorensen says, "because you still don't really know for certain what course chemical reactions will take until you get into the lab and do it. You can be very successful in chemistry reasoning by analogy. We know that this reaction takes this course, so this experiment is analogous to that one, and therefore we should get a similar reaction. A lot of times, that's the way it is."

And a lot of times, it's not. A month earlier, one of his graduate students was performing an experiment with an expected outcome. Except it didn't happen. "It surprised all of us by turning out to be something useful, much more than we thought it would."

It wasn't necessarily the first surprise in Sorensen's life. The first one probably occurred when he was an undergraduate at Syracuse University, planning to be an optometrist. Then he took organic chemistry, and forgot all about optometry. It was the three-dimensionality of it that got to him, he says, the invisible architecture of those really useful molecules.

From Syracuse, Sorensen moved on to doctoral work at UCSD, where he was fortunate to become a member of Dr. K.C. Nicolaou's team. Nicolaou, one of the world's top synthetic chemists, was working on the total chemical synthesis of taxol, a scientific problem that eluded scores of research labs for 20 years, and that he solved in 1994. Nicolaou, who also first synthesized the neurotoxin responsible for the devastating red tide epidemics, is chairman of the Department of Chemistry at TSRI, a professor in The Skaggs Institute and a professor at UCSD.

After graduation, Sorensen became a National Science Foundation postdoctoral fellow at Memorial Sloan-Kettering Institute for Cancer Research in New York under another internationally recognized chemist, Samuel Danishefsky, Ph.D. As Sorensen makes clear, his scientific background is homogeneous, both in training and in influence. Almost from the beginning, he was pointed in the direction of organic chemistry and The Scripps Research Institute.

THE PATHWAY HEADING TO FUMAGILLOL

"I heard that lecture in the spring of 1997 on angiogenesis," Sorensen remembers. "And I heard him describe fumagillin, the first natural product to have been discovered to have this inhibiting activity. I immediately went back to my lab, looked up the structure, and realized this was exactly the kind of novel molecule I was interested in studying."

The next step in the process moved to the Japanese pharmaceutical industry, where researchers quickly developed nearly 100 different varieties of the fumagillin molecule. In the process, they found TNP-470, a chemical relative with potent angiogenesis inhibiting properties, a small molecule that looked promising in its ability to kill tumors.

So, when Sorensen was asked to join the faculty and form his own laboratory at TSRI, fumagillin was one of the first things he worked on. What he was looking for was a pathway of reactions, a sequence of events in which you could take abundant molecular building blocks and develop a chemical strategy to transform them into a more potent product. The key was finding a concise transformation sequence to save the time and expense of producing the molecule in quantity. In two years, Sorensen and his students managed to develop a shortened pathway leading to fumagillol, the direct precursor of fumagillin, TNP-470, and a wide range of related structures. What they are hoping to do next is create an entire family of analogue structures that are not accessible from the natural fungus itself.

"As students of chemistry, we think a lot about reaction channels that nature makes use of to create useful architecture," he explains. "We look to nature for ideas that may be profitable for synthesis. Nature is the master of creating complicated, useful molecules, so our broad goal is to approximate the efficiency in the way nature solves these chemical problems but go one step further. Our lab is designed to challenge the underlying hypotheses about the origin of various structures in nature and see if we can figure out a more concise way."

Small, highly focused, and efficient, Sorensen's lab certainly looks like a good bet for the future. Expectations are high and he admits to a certain amount of pressure to do good\ science. With a small lab, the focus is on a fewer number of research projects, so what the lab might lack in breadth, it easily makes up for in depth and concentration. Foremost in his mind is the responsibility to make a contribution. TSRI has made that a real possibility.

"Scripps has supported us tremendously," he says, "and we're very grateful for that support. Without it, we couldn't have gotten started, wouldn't have the lab space or the outstanding facilities. We're a young lab and to have this kind of support available has made all the difference in our work."

In addition to fumagillin, Sorensen's lab is involved with another molecule, one with a structure of extraordinary elegance and complexity -- and with the rather prosaic nomenclature WS9885B. The behavior of this molecule with the uninspiring name is much like that of taxol, a throwback to Sorensen's baptism at TSRI. What makes it so effective, he says, is its natural ability to arrest cell division by interfering with the mechanics of the process. It stops the cell cycle, which makes it particularly destructive to cancer cells, where the cell cycle itself has accelerated out of control. The new compound was discovered in the course of a broad search for taxol-like molecules, although it is still unclear whether its remarkable activity will be effective in humans.

"Some people think of chemical synthesis as an art," Sorensen says. "If you look at any given problem, fumagillin, for example, there are countless ways to create a molecule like that, but certain pathways will be better than others. So the way you achieve your objective is very important today, much more important than it was thirty years ago. People are not really surprised anymore that you can create a structurally complex molecule in the lab. Now, they want to know how you did it.Did you do it in a way that might have a positive effect on people engaged in biomedical research? Did you do it concisely?"

FORM AND FUNCTION

Conciseness is the way the new world of synthetic chemistry works, where formation is as important as function. In some ways, it takes precedence, especially in the highly competitive world of drug development. The most sublime discovery in the world means little to future cancer patients if it cannot be produced in commercial quantity quickly and at less cost.

Science has been heading in this direction for a while. The great thing is that Erik Sorensen is already there.