Profile: Clayton Heathcock
his office on a gloriously clear Northern California day, Clayton Heathcock
was explaining the evolution of organic synthesis and the challenge of
his new project.
“In the 1960s,
we were pushing the envelope in synthesizing compounds, seeing what could
be made. By the 1980s it was clear that, given enough time, we could make
pretty much anything we wanted, but sometimes in only very tiny amounts,
which was not useful to anyone,” said Heathcock. “Now the challenge is
to synthesize compounds in significant enough amounts to be useful, say
a jarful of material that can be used to treat cancer patients.
products are important targets for organic chemists because many of these
compounds can be used as drugs against nasty diseases like cancer,” he
with the paper sludge
“A byproduct of the caustic digestion is a thick sludge composed of terpenoids and steroids. Because it was a complex mixture, it was simply burned to create heat that was used to power the digestion process.
undergraduate class work, I knew that the steroids in this byproduct,
called ‘tall oil,’ were potentially valuable. So when I went to graduate
school [at the University of Colorado, Boulder, where he studied with
Alfred Hassner], I studied steroid synthesis so I could turn material
like that discarded byproduct into a valuable commodity.” He became a
master at synthesizing intricate, complicated compounds and followed his
studies at Colorado with a postdoctoral stint at Columbia under the illustrious
products at Berkeley
arrived at Berkeley in 1964 and immediately focused on natural products,
continuing his goal of creating valuable steroids. “The very essence of
natural product synthesis is that it is a problem with multiple solutions.
It’s the challenge of the synthesis, the logic and the planning, that
is sometimes more appealing than the actual product.”
career has been characterized by creative approaches to creating natural
products. He has planned and directed the synthesis of almost fifty natural
products. “One of my most enjoyable projects—achieving acyclic stereocontrol
through the aldol condensation—started out as a very classic steroid synthesis
approach, going from step A to step B lockstep. As we progressed, we learned
more about a group of related compounds and figured out a method that
we suspected the plants themselves were using. We made all five rings
in one simple process—a synthetic shortcut that was very rewarding,” he
explained. This was a novel approach: chemistry based on biology. “It
turned out to be a useless compound, and we still don’t know whether the
plants actually use this method,” he said with a laugh, “but our approach
served as an inspiration to other scientists.”
target is spongistatin 2, which depolymerizes tubulin and inhibits cancer
cell growth. Spongiostatin compounds (originally isolated from an Eastern
Indian sponge) have been synthesized before, but only in tiny amounts.
“To achieve a multi-gram synthesis of spongiostatin 2, we have to pursue
over 100 separate reaction steps to make it as cheaply and efficiently
as possible. We want to make enough of the product so that it can be evaluated
for safety and efficacy against various cancers. If we are successful,
this can spur companies and investors to either farm sponges or to isolate
the genes responsible for the protein machinery that manufactures spongiostatins
in sponges, insert the genes into bacteria, and set up a bacterial production
‘factory,’ ” he explained.
He has also
advised almost 150 graduate students and postdocs, some of whom have discovered
important drugs (see below) both in industry and academia. “Clayton has
this remarkable ability to get young scientists to open their eyes and
see the bigger picture,” notes a former student.
to the dogs
to just show dogs, Heathcock is also very active in the Rhodesian Ridgeback
Club of the United States, serving as its president from 1999 to 2000
and is currently the organizer for the 2004 Rhodesian Ridgeback World
Congress, which will be held in Forth Worth, Texas, in September of this
Just the latest project in a career filled with academic adventure and success.
A number of students from Heathcock’s lab have made waves in the drug discovery field, synthesizing numerous potentially-lifesaving therapies. To name a few: