Chapter 4

Application

Waking a half an hour before dawn, I found my anchorage quiet and peaceful. I could make out the purposeful roar of cars and trucks on U.S. 1, a mile behind Coconut Grove. Feeling clarity of purpose that had been absent for years, I knew my decision was made. Over a bowl of cereal wetted with condensed milk, a hard-boiled egg and a cup of coffee, I studied the brochure with growing enthusiasm.

     The Old Man seemed to know my decision before I crossed his threshold.

     "Iím ever so pleased that you have decided to have a go at it! Of course, our conversation of last night really didnít take place . . . just rest assured that Iíll keep up my end of the bargain. Yes, I am so pleased! And I do think that it will benefit your professional advancement. Of course, the first thing to do is to apply to the department. Consider yourself excused today so that you can get busy with it."

     "So I start working on the application this morning?"

     "Yes, with all due speed. Once accepted in Pharmacology, you can tender your resignation to me, and we can proceed as discussed. You would need to be available here three evenings per week for your Ďindependent contractorí duties."

     "What if they donít have a slot for me in September?"

     "Well, you could perhaps suggest starting with a single course. Getting the camelís nose under the tent, so to speak."

     "Sounds fine."

     "Yes, swimmy! One final thing. We shall have no more communication on these matters in my office ó deniability and that sort of thing. Nothing should appear irregular. But Margaret and I would be most delighted to have you for dinner as soon as you learn where you stand with those folks."

     Yes, Bryan Medical School was a "scant 300 yards" from our facility. It occupies a wide and long nine-story building, painted in the same battleship gray as all the other buildings of the Dade County General Hospital complex. The portal to my future was a pair of glass doors obscured by the same corrugated sheet metal canopy system which covers all of Dade Generalís walkways.

     I opened the door and stumbled onto a guard station where I was asked to show my badge. My Medical Examinerís badge didnít do the trick. It just made the guard a little suspicious. The Medical School belongs to a private university and is not connected to Dade County General Hospital or the M.E. Office. The guard called ahead to the Graduate Office and then gave me directions. It was a small office, staffed by a single worker.

     Half an hour later, I was back at the M.E. facility working on my application packet for Pharmacology. By two oíclock I had completed it and confided my aspirations to Doris. She insisted on seeing the application package and suggested some modifications which made it look more professional. She was able to drag up a copy of my Swarthmore transcript, going back to my original application to the M.E. Office.

     With two copies in hand, I went over to the Medical School. I gave the originals to the woman at the Graduate Office and was given directions to the Pharmacology Office on the fifth floor to deliver the copy.

     I quickly did my homework, reading the page of the brochure which described Dr. Gordon Taylor, the head of the graduate program. His picture showed the sternest, most unforgiving face of the whole bunch. He had received his Ph.D. from the University of Cambridge in 1965. His research topic was the "electrophysiology of squid axon," which meant that he stuck electrodes in squid nerves to study their signalling. I knew that the squid axon was a "good model" for the nerves in the brain. Taylorís two cited publications had to do with "noise analysis of the sodium channel at low temperature."

     On the fifth floor, I found a cluster of Pharmacology mailboxes and searched for Taylorís name. Someone was waiting behind me. I quickly put the letter in Taylorís box and stepped to the side. With one spritely step and a long reach, the person pulled out my letter. It was Taylor himself. His eyes, blue-gray and penetrating, were as stern as in the brochure, but in real life he looked slightly comical. Maybe it was his rumpled shirt or his dark brown hair, so thick and unruly on the bottom but thin and wispy on the top.

     Half embarrassed, attempting to break the ice, I said, "Now there isnít any question that youíve gotten my letter."

     "No. Now the only question is as to its contents," he said, stroking his well-trimmed beard in mock contemplation. "Let me think: Itís too early to complain about my annual lectures on nerve conduction being too hard. The Medical Sophomore Course hasnít started yet."

     With this, he broke into a boisterous laugh and a sympathetic smile. He spoke with an unmistakable English accent, undiminished by some 25 years in Miami. Although his enunciation was like Westleyís, his delivery was quite different. Westleyís words resonated softly in his upper nasal passages; Taylorís words resonated loudly in his chest.

     "No, Iím not a medical student. The envelope contains my application for admission to your Ph.D. program," I said nervously.

     "Just one week before the start of the semester! Well, just in time for the new campaign. We are always looking for cannon fodder!"

     He sounded like a British sergeant major mustering a squad in Sudan. Almost every sentence was punctuated by boisterous laughter.

     "I know that the timing is tight," I replied. "If you have to delay consideration of my application until January ó "

     "By no means! Step with me into my recruiting office. Letís place your pint of ale before you and get you to touch the Kingís Shilling!"

     While tearing open the envelope and skimming its contents, he ushered me down the hall, all the while keeping up a curious line of stentorian chitchat. He led me into a laboratory, better described as an attic filled with scientific paraphernalia ó hand-assembled electronic consoles, connected by tangles of wire to 1950s vintage oscilloscopes, microscopes sitting on tables, with small glass Petri dishes and bundles of needle-thin glass pipettes, all enclosed in large screen-wire cages.

     Dr. Taylorís office could have once been an oversized mop closet. His desk fit snugly against three walls. Over it hung several wooden shelves, bolted into the wall and sagging from the weight of hundreds of pounds of books. What floor space remained was sacrificed to two file cabinets on which tottered a three-foot stack of Nature magazines.

     Taylor entered the office first and sat down with his chair facing outward and his back to his desk. He indicated that I should take his "guest chair," a lab stool with wheels. With me sitting in the middle of the narrow doorway, there was just enough room for the two of us to converse at a less-than-comfortable distance. The stack of Natureís towering over me might have required no more provocation than one more boisterous laugh to bury me in an avalanche.

     "Well Mr. Candidi, your applicationís quite interesting," he said, flipping through the papers. "Some lab experience, I see. Oh, yes, hereís the transcript. Swarthmore. Fine college. Chemistry and physics. Finished in 1986. Been out for a while. Late bloomer, are you? Good grades, though. Awards, honor societies and a senior thesis? Weíll need an original transcript, of course."

     "It has been ordered."

     "Whatís this? A post office box as an address?"

     "Itís the most reliable way to get my mail," I equivocated.

     "And I see you had quite a bit of chemistry. Good grades there too. But no Graduate Record Exam score. What a shame."

     "I took the test right after graduating and did well on it. I have ordered the results to be forwarded to you."

     "Yes, yes. Instrumental analysis, application of chemical principles to life science. Excellent. And your essay: ĎScience is a most interesting and useful human pursuití; you work on Ďultrasensitive methods of quantitative analysis of organic chemicals.í And you read journals such as Science and Nature. Did you, by chance, see in the latest Nature ó that exciting article on prions?"

     "No, but I read about them a couple of years ago in the Scientific American. I subscribe to it."

     "Hobbies of sailing, photography and literature? German and Spanish as foreign languages? Sprechen Sie Deutsch?"

     "Jawohl." (I barely spoke it.)

     "And Spanish just as well, no doubt."

     "Es mejor," I said. I hadnít written that I was fluent in Cuban Spanish. I also omitted any mention of my membership in the Mensa Society.

     "Well, fine. And you write that you Ďwish to become an academic research scientist or an industrial scientist engaged in drug discovery and development.í Now I need to ask a few questions. Are you applying to medical school? Do you harbor any secret desire to become a physician?" His blue-gray eyes scanned me carefully, waiting for an answer.

     "No. I am more interested in studying things in depth. Iím going for the Ph.D., not the M.D." This pleased him.

     He lectured me that getting a Ph.D. is a long arduous process requiring high-level thinking.

     "I think I can do it. I have good quantitative and deductive skills. I can express myself pretty well. I have a broad range of interests . . ."

     "Yes, I see," he said flipping back to my transcript. "You also received an ĎAí in philosophy. Say, tell me, Mr. Candidi, what philosophy did they teach you in that course? That it is the Best of All Possible Worlds!" His laugh rattled the file cabinets.

     A flash of inspiration furnished a reply. "Yes, thatís exactly what they did teach. The profís name was Dr. Pangloss." Dr. Taylor smiled at my snide answer, so I upped the ante. "At this point could I ask you how well am I standing up to the Grand Inquisitor of Lisbon?"

     This brought out another booming laugh. His chest heaved, and he literally bounced in his chair. The stack of Nature magazines didnít fall. It was my lucky day.

     "Mr. Candidi! You are the right fellow who has come at the right time."

     He sent me to interviews with two colleagues.

     I quickly consulted the brochure before walking into the lab of Dr. Robert Sturtz. He earned his Ph.D. in 1987 from Rensselaer in Upstate New York, had been a post-doctoral fellow at Cal Tech. He was studying how growth factors turn on the genes in "fibroblast" cells to make them multiply. So he should know what makes skin grow back over a wound.

     Dr. Sturtz had a narrow head, short curly black hair and seemed to be in his thirties. Standing next to his technician in front of a bank of compact fluorescent lights, he held what looked like an X-ray negative with a dozen oversized bar codes ó the type that the laser scanner reads at the supermarket ó but larger and longer. A bumper sticker on the door asked, "HAVE YOU READ ANY GOOD DNA LATELY? Eta Chemical Company." I guessed that was exactly what Sturtz was doing ó reading DNA.

     He handed the film back to the technician and said, "These sixty-six bases are fine. Add them to the sequence and then analyze the next stretch."

     He greeted me with a self-satisfied smile, and we went into his office. While heavy-metal rock music wafted in from the adjoining lab, Sturtz read my application. He intimated that I didnít have enough biology to study pharmacology.

     Dr. Robert Gunnison from Stanford Medical School (Ph.D., 1988) and U.C. Berkeley (post-doctoral) wasnít any friendlier. I figured he was also in his thirties, but his narrow, gaunt face could have belonged to a 50-year old. Science can do that to you. While he read my application, I read his blackboard:

     Androgen ó> Nucleus ó> Receptor ó> mRNA ó> Protein ó> ???

     Across from his desk was a poster of a long-haired girl in a bikini, riding a sailboard, with everything blowing and bouncing in two-foot waves. It was captioned:

     "CALIFORNIA GIRL, Catalina Sailboards, San Diego, CA."

     Gunnisonís lab uniform was a Hawaiian shirt over an old pair of faded blue jeans with sandals. He subjected me to some stiffly-phrased questions about my education and listened impatiently, stroking his closely-cut blond beard as I answered. Luckily, his phone rang, putting an end to the interview.

     I handed back my application to Dr. Taylor. He had been staring at a computer screen, manipulating a joy stick like he was playing a video game. A single line traced across the screen, drawing rock formations like in a Roadrunner cartoon.

     "Each one of these blips is the electric current going through a single sodium channel in a nerve membrane," he said in a much softer and more natural voice.

     I had enough dilettante knowledge to understand in a general way. Dr. Taylor could actually "see" the activity of a single molecule. He explained the workings of his "microelectrodes" and sensitive amplifiers, and how he digitally-recorded the data on "miles and miles" of tape when squid were in season up in Woods Hole, Massachusetts. "You see, there is limited time and a limited number of squid. So you run day and night to stock up on data. Rather like a cow hastily devours grass in the meadow and chews her cud elsewhere." The stentorian voice had returned. "You might say that I come back here to ruminate." The boisterous laugh returned in full strength.

     My physics background proved strong enough for me to play the interested student to his lecture on "open state probability," "noise analysis" and "ensemble averaged behavior." He warmed up to me. Slowly, the conversation returned to my application. I was in luck, they were having a faculty meeting next Monday. They would probably render a positive decision at that time, pending transcripts and GRE score.

     The next day was a Friday. The M.E. lab was still doing a lot of extra work on what I guessed was Cooperís blood samples, but Burk told me to stay away from it. I spent the dead time browsing the pharmacology brochure. Based on their scientific research, the deadliest prof was George Ashton, M.D., an aristocratic-looking full professor who was specialized in neurotoxins.

     Doris always read the Miami Standard on her coffee breaks. When I went to ask if she had copies from the last several days, she was making a long-distance call. I waited around and overheard an interesting conversation. She was calling the Institute for Scientific Information in Philadelphia, ordering for Dr. Westley all the scientific publications of Dr. George Ashton. No, she didnít want to order publications from any other authors.

     Doris had the right newspapers. In a three-inch column under "Death Notices," I learned that Charles David Cooper, Ph.D., had tragically and unexpectedly passed away, being survived "by his wife, Dr. Jane Goddard Cooper and two sons, Charles D. Cooper, Jr. (22), and James L. Cooper (19)." The Notice stated that he was a prominent molecular biochemist, Chairman of the Department of Pharmacology at the Bryan Medical School and that he had made major contributions to the understanding of heart disease. He was a member of many community organizations and was a vestryman at St. James Episcopal Church. His funeral was to be held there and his ashes were to be "scattered at sea." Instead of flowers, his friends were asked to make a contribution to the Florida Affiliate of the American Heart Association, in his name. I hoped that the Old Man had gotten some good blood and tissue samples before the cremation.

     My Friday evenings are usually devoted to bar hopping in Coconut Grove, but this time my heart wasnít in it. No use searching for girls in the bar scene when graduate study promised to introduce me to girl scientists. And I might as well get a head start on the investigation.

     Early the next morning I was dodging cars and the dangling air roots of the enormous ficus trees along the narrow and historic Main Highway in Coconut Grove. Then I pedaled north through tropically overgrown "South Grove," crossed a dirty carbon monoxide canyon called U.S. 1, and took in the well-manicured lawns and expensive Mediterranean-style houses of stately Coral Gables.

     The Coral Gables Library is a historic building of quarried coral. I locked my bike by the fountain and entered through the massive wooden doors. Microfilms of the Miami Standard yielded what I was looking for: a Sunday supplement story describing how an upstate coroner may have killed his wife with an injection of potassium chloride. I checked a physiology book and was pleased to learn that high concentrations of potassium in the blood mess up the electrical impulses that make the heart contract.

     It wasnít a particularly clever murder because the potassium had to be injected. If you take it by mouth it upsets your stomach and you throw up. So the unimaginative upstate coroner injected his wife, leaving a needle mark which was detected.

     A back issue of Time magazine yielded a slightly more clever example of murder by a physician. This guy injected his wife with the drug called "succinylcholine." The physiology book told me that the compound works like acetylcholine, opening up the sodium channels, but overstimulating them so they eventually shut down. At low doses it relaxes your throat so the anesthesiologist can insert the breathing tube. At high doses, it relaxes your diaphragm muscles and you canít breathe at all. The wife died of asphyxiation.

     But the coroner noted the needle marks and became suspicious upon learning that the doctor was an anesthesiologist. Hell, I knew enough biology to study pharmacology! As a further exercise, I looked up "ricin," the poison that the Bulgarians put in the BB to kill the BBC journalist. I learned that it is an "enzymatic peptide" that cuts in half the "ribosome" inside the cell. And, of course, it had to be injected to be lethal.

     Did all protein toxins have to be injected? I vaguely remembered a Scientific American article on "proteins as drugs" and found it on the shelf. The article said it was virtually impossible to deliver proteins orally. The protein would have to be modified so that it could cross the intestinal lining which was there for the express purpose of keeping foreign proteins from getting into the blood stream. So the Old Man was right. The article said that there was a tremendous need for an oral delivery form for insulin, because most diabetics hate to inject themselves.

     So I should concentrate on nonprotein molecules which do not get digested. I got real excited about the project ó too excited for my own good, actually.



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