By the wee hours of Thursday morning, Edward and Eleanor were rewarded by the image of the entire molecular structure appearing on a computer screen in virtual three-dimensional space. The achievement had been the product of new structural software, supercomputer capability, and hours of heated argument between Edward and Eleanor as each played devil’s advocate with the other.
Hypnotized by the image, Edward and Eleanor silently watched as the supercomputer slowly rotated the molecule. It was in dazzling color, with the electron clouds represented by varying shades of cobalt blue. The carbon atoms were red, the oxygen green, and the nitrogen yellow.
After flexing his fingers as if he were a virtuoso about to play a Beethoven sonata on a Steinway grand piano, Edward sat down at his terminal, which was on-line with the supercomputer. Calling upon all his knowledge, experience, and intuitive chemical sense, he began to work the keyboard. On the screen the image trembled and jerked while maintaining its slow rotation. Edward was operating on the molecule, chipping away at the two side chains he instinctively knew were responsible for the hallucinogenic effect: the LSD side chain and the scopolamine side chain.
To his delight, he was able to remove all but a tiny two-carbon stump of the LSD side chain without significantly affecting either the three-dimensional structure of the compound or its distribution of electrical charges. He knew altering either of these properties would dramatically affect the drug’s bioactivity.
With the scopolamine side chain it was a different story. Edward was able to amputate the side chain partially, leaving a sizable portion intact. When he tried to remove more, the molecule folded on itself and drastically changed its three-dimensional shape.
After Edward had removed as much of the scopolamine side chain as he dared, he downloaded the molecular data to his own lab computer. The image now wasn’t as spectacular, but was in some respects more interesting. What Edward and Eleanor were looking at now was a hypothetical new designer drug that had been formed by computer manipulation of a natural compound.
Edward’s goal with the computer manipulations was to eliminate the drug’s hallucinogenic and antiparasympathetic side effects. The latter referred to the dry mouth, the pupillary dilation, and partial amnesia both he and Stanton had experienced.
At that point Edward’s true forte, synthetic organic chemistry, came to bear. In a marathon effort from early Thursday to late Thursday night, Edward ingeniously figured out a process to formulate the hypothetical drug from standard, available reagents. By early Friday morning he produced a vialful of the new drug.
“What do you think?” Edward asked Eleanor as the two of them gazed at the vial. They were both exhausted, but neither had any intention of sleeping.
“I think you’ve accomplished an amazing feat of chemical virtuosity,” Eleanor said sincerely.
“I wasn’t looking for a compliment,” Edward said. He yawned. “I’m interested to know what you think we should do first.”
“I’m the conservative member of this team,” Eleanor said. “I’d say let’s get an idea of toxicity.”
“Let’s do it,” Edward said. He heaved himself to his feet and lent Eleanor a hand. Together they went back to work.
Empowered by their accomplishments and impatient for immediate results, they forgot scientific protocol. As they had done with the natural alkaloid, they dispensed with controlled, careful studies to get a rapid, general data to give them an idea of the drug’s potential.
The first thing they did was add varying concentrations of the drug to various types of tissue cultures, including kidney and nerve cells. With even relatively large doses they were happy to see no effect. They put the cultures in an incubator so that they could periodically access them.
Next they prepared a ganglion preparation from Aplasia fasciata by inserting tiny electrodes into spontaneously firing nerve cells. Connecting the electrodes to an amplifier, they created an image of the cells’ activity on a cathode ray tube. Slowly they added their drug to the perfusing fluid. By watching the neuronal responses, they determined that the drug was indeed bioactive although it didn’t depress or increase the spontaneous activity. Instead the drug appeared to stabilize the rhythm.
With mounting excitement, since everything they did yielded positive results, Eleanor began feeding the new drug to a new batch of stressed rats while Edward added the new drug to a fresh synaptosome preparation. Eleanor was the first to get results. She was quickly convinced the modified drug had even more calming effect on the rats than the unaltered alkaloid.