The Darwin Awards Next Evolution: Chlorinating the Gene Pool (14 page)

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nternet surfers and tabloid readers are fascinated by the rich and famous. This tale concerns a young biochemist fascinated with the slimy and contagious! Dr. Herbert Boyer was investigating a common bacteria identified in 1885 by pediatrician Theodor Escherich, who was studying the tragically high rate of infant mortality due to diarrhea when he isolated a rod-shaped microbe in a residue we need not dwell on. The bacteria he discovered now bear his name:
Escherichia coli
, or
E. coli
for short.

You may recognize
E. coli
from the news. Hardly a month goes by without a health advisory issued by the CDC about a new outbreak. Beef, spinach, lettuce—any number of innocuous foods sitting in the crisper of your refrigerator may harbor the killer. There are hundreds of strains of
E. coli
. Most are harmless. But some strains produce potent poisons with the power to cripple their host and bring on the kind of misery that any dehydrated tourist bent over a Mexican toilet can understand. And a few strains are so deadly they could be classified as biological weapons! Still, there’s a kinder side to this ubiquitous microbe, a gentler side, a side that serves humanity. Odds are good that one day the humble
E. coli
will serve you too.

After their discovery in 1885
E. coli
were found in the small intestines of virtually every warm-blooded animal. Several pounds of the bacteria reside in the gastrointestinal tracts of large animals like horses, German shepherds, and, yes, people too. Most strains cause no harm. But researchers came to realize that some strains of the bacteria rampage through the unfortunate host, causing symptoms ranging from lingering malaise to rapid death.

Scientific interest intensified.

Because
E. coli
are widespread and easy to keep alive in the lab, they soon became the most studied microbe in the world. Libraries were filled with sketches and chemical equations describing them. Our understanding of the molecular intricacy of these one-celled creatures grew rapidly.
E. coli
was not a primitive life-form from a forgotten slimy crevice. The bacterium was an exquisitely evolved animal, every bit as flexible and cleverly constructed as are we giants of muscle and bone.

They taste the world around them, run the data through a molecular supercomputer, and reconfigure their metabolism to use those nutrients that happen to be available. They build sophisticated defenses against almost any deadly substance that wanders into their domain. When necessary, most can build a flagellum—a tiny motorized propeller that rotates thousands of times a second—and zoom around like high-tech submarines. When food and water are scarce,
E. coli
can even go into stasis (suspended animation)—for years, if necessary.

These transformations are beyond any metamorphosis possible for plants or animals. But
E. coli
reproduce in a matter of hours, so they have had far more relative time, at least as measured by individual generations, to evolve than multicellular plants and animals. To put the talents of
E. coli
into perspective, imagine a herd of horses starving in a drought. If horses were as mutable as
E. coli
, one would morph into a Bengal tiger and eat the rest, and when that food was exhausted, it would sprout wings and fly away. If necessary, it would burrow into the earth and hibernate until rains brought the meadows back. Then it would become a horse again, happily munching on green grass.

When scientists began to sequence DNA, the very code of life,
E. coli
was among the first to be scrutinized. That’s when another surprising microbial ability was noticed.
E. coli
were exchanging genes! That wasn’t supposed to happen.
E. coli
reproduce by splitting in two, and the daughter cells are identical to the parents. Sex in single-celled organisms? Unthinkable!

Dr. Herbert Boyer was studying the exciting details of gene exchange when he had a revolutionary idea: If genes from one
E. coli
could be transplanted into another…could the genes
of a different species
be transplanted into the bacterium? To insert foreign genes Boyer enlisted the help of a plasmid.

A plasmid is a small ring of DNA that carries useful genes. Plasmids are the means by which bacteria swap genes. The realization that bacterial genes are kept not only in the chromosomal DNA, but also on small, transferable rings of DNA, was revolutionary. Plasmids behave very much like the remnant of an independent microbe that struck up a partnership with the ancestral
E. coli
. In return for food and shelter plasmids offer their host a library of useful genes.

The plasmid has an unusual ability. It can acquire random genes from a passing virus, or from the chromosomal DNA of bacteria, and make these genes available to other bacteria. When a bacterium must radically reconfigure itself to survive changing conditions, adaptive genes are often stored on the plasmid. A familiar example is antibiotic drug resistance, which is caused by a protein that inactivates the antibiotic. The gene for the protein, located on a plasmid, is easily transferred between bacteria. Plasmids give
E. coli
the flexibility to quickly adapt to changing conditions.
E. coli
has evolved to evolve, via the plasmid.

Boyer realized that he didn’t have to insert a gene into the chromosome of the
E. coli
, a tricky maneuver with a low success rate. Instead, the plasmid would do the work for him. Boyer merely had to isolate a plasmid, coax it into accepting a gene of his choosing, then put it back into the
E. coli
. Plasmids are adept at moving useful genes from one
E. coli
to another, and this ability was exactly what Boyer wanted. Once inside, the plasmid should theoretically produce the protein coded by his foreign gene.

Sounds easy? It took thousands of lab hours and years of work before Herbert Boyer’s first gene-engineered
E. coli
was confirmed to be a success. By the late 1970s Boyer had created mutants! He knew how to insert genes from wholly different creatures, with a variety of functions, into
E. coli
. If the foreign gene coded for a protein, the bacteria would churn out the substance, while the plasmid was powered, propagated, and protected by the microbe.

Dazzled by the commercial possibilities, Boyer and business friend Robert Swanson invested five hundred dollars each to create a fledgling company and patent this process. And for his invention to be lucrative Boyer decided to program his next designer bacteria to produce a substance with a high demand. A chemical that people wanted and, better yet, needed. He quickly settled on his target: insulin.

Insulin is a small peptide hormone composed of fifty-one amino acids. At the time diabetics were given insulin purified from large mammals such as horses and pigs. It controlled blood sugar levels, but not as effectively as human insulin. Complications from diabetes in general and animal insulin in particular could lead to devastating tissue damage, ruining eyes, heart, liver, or extremities. Animal-derived insulin could trigger rare but life-threatening allergic reactions, yet the only source of human insulin was minuscule (and expensive) amounts obtained from living humans or human cadavers. If Boyer could coerce
E. coli
into making the genuine human version, the mutant bacteria could be grown by the billions in large fermenter vats. Doses of pure human insulin would be unlimited!

And it worked. Humulin is now used by millions of diabetics worldwide. Because it is an exact replica of human insulin, it adds years of life while avoiding the serious side effects of nonhuman insulin. For diabetics who could not tolerate insulin from animal sources, it was the stuff of life itself.

Boyer and other researchers have since created mutant
E. coli
that churn out many useful proteins: human growth hormones to treat dwarfism, blood thinners for heart patients, and an array of other substances. Custom-engineered plasmids themselves have become a robust and lucrative subspecialty in the booming designer microbe industry. The microscopic bacteria have become a laboratory workforce, efficiently and reliably making lifesaving drugs and proteins used for medical research.

For his pioneering contributions to genetic engineering and medicine Herbert Boyer has received academic distinctions. He was awarded the National Medal of Science in 1990. The Yale School of Medicine named its Boyer Center for Molecular Medicine after him. He shared in the prestigious Lemelson–MIT Prize in recognition of his invention. Dr. Herbert Boyer’s advances may one day lead to a Nobel Prize.

Oh, and don’t forget the small company Boyer and Swanson started with a thousand dollars. They called it Genetic Engineering Technology, or Genentech for short. The two-man firm had been struggling on the edge of bankruptcy, but the promise of Humulin changed all that. In 1980 Genentech went public, using the ticker symbol DNA on the NYSE. The thousand dollars became $130 million overnight, and their shares are worth billions today. Amgen, Biogen, Genzyme, and ImClone rode on the coattails of Genentech’s success. Gene-swapping techniques created an entirely new industry, biotechnology, which now employs thousands of highly trained scientists.

Herbert Boyer started out looking into the slimy and contagious, but because of the wealth and recognition he earned, Dr. Boyer’s presence would not be amiss on
Lifestyles of the Rich and Famous
!