Dancing With Myself

by Charles Sheffield

  “We’ll be taking this up again next semester,” I began at last. “But given the confusion in some of your answers, I’m going to hit this one more time and let it sink in over the summer. Cell division can get complicated, but the principles fit on one blackboard. Basic rule: cells divide in two fundamentally different ways. Mitosis means that the DNA in the cell is duplicated exactly, to give double the amount. Each chromosome is exactly copied in the process, and then the cell goes on to divide, and become two cells. Mitosis is non-sexual.” I wrote those words in the first column and underlined them. “When plants or animals lacking separate male and female forms reproduce, their DNA duplication has to be done through mitosis. Look at that T in the middle of the word, miTosis, and remember.” I wrote: If you have TEA, you don’t have sex.

  “Unfortunately, the textbooks often don’t help. They refer to cells produced following mitosis, through simple cell division, as daughter cells. That is a bad name. They are better called neuter offspring.”

  While I was talking I looked around the class. Half a dozen students, including a Chinese girl and Italian twin boys in the front row, were hanging on my every word. Needless to say they had been having no trouble at all. The focal point of classroom ignorance was near the back, where three T-shirted youths drooped over their desks in attitudes of extreme exhaustion or boredom. They stirred and nudged each other when I mentioned the word sex, but no matter what I said they would go out of the room as uninformed as when they came in. It was no consolation to realize that their parents were paying fourteen thousand a year for the privilege of having their children learn nothing.

  I sighed, and went on. “Meiosis, on the other hand, only takes place in sexual organisms. And it’s easy to see why it’s necessary. When anything, from a mosquito to a hippopotamus, develops by fusion of a sperm and an egg, the DNA from both is in the offspring. So if the sperm cell and the egg cell each had the same amount of DNA as other cells of the body, the offspring would have twice too much DNA. To prevent that, there is another form of cell division called meiosis. Each of you is a product of meiosis. You all had a father and a mother, and half your DNA came from each of them. In meiosis, cells are produced with half as many chromosomes and half as much DNA as a normal body cell. These are called gametes—that’s either the sperm or the ovum—and when they merge to make a fertilized cell that’s a zygote….”

  We had been through this six times in class. How was it possible for students to miss the point, over and over again? Was I that bad a teacher? I stared at seventeen faces, half a dozen following me, half a dozen yawning or doodling, the rest as perplexed as if I were addressing them in Mandarin.

  Then I wondered if it was all relative. I was groping too, and just as out of my depth. Maybe I was missing some obvious point in my research, shunning the self-evident as badly as my dimmer class members. (Last year one of my students had gone half a semester in Cell Biology before I found that he didn’t know what a helix was. Others told him it was a sort of spiral, and he’d visualized the flight of a football.)

  While I went through the description of meiotic cell division and homologous chromosome pairs, my mind wandered back to our failing experiments.

  Oscar and I were trying to create a universal DNA converter—a “general DNA eater,” unlike anything in nature. If we were successful, the organism we were working on should also handle viral genetic material, so our NIH grant was not illogical. Our starting point had been the most basic observation in molecular biology, that a DNA molecule does one thing superbly well: it copies itself, with a tiny error rate. It also, through the intermediary of the RNA molecule, controls the workings of the cell that contains it. Every cell uses the information in its own DNA, both to run operations and control cell division.

  Viruses are nothing more than parasitic chunks of DNA or RNA, wrapped in a coat of protein. Once a virus enters a cell it makes use of the DNA and protein “production line” there to form many copies of itself, until the cell bursts open and releases a slew of new viruses.

  So why don’t you die, when you get a viral infection like polio or the common cold? You don’t, because your body has its own immune system, a set of “defensive” cells that mop up viruses—eat them—and dissolve their alien DNA or RNA. The terrible thing about AIDS is that HIV—the Human Immunodeficiency Virus—infects, and destroys, the cells of the body that are supposed to protect us.

  Oscar had had the first idea. Then I thought of a way to build the experimental system. When it showed promise, we wrote our proposal. Our “DNA converter” changed DNA in the body to a “template DNA form” that we provided. When a DNA molecule begins to make a copy of itself, it unravels the ends of the double helix, to separate and leave exposed a purine or pyrimidine pair. New purine and pyrimidine molecules (adenine, guanine, cytosine, or thymine) attach themselves to make two new pairs and start production of a new double helix. Oscar had argued that the place to attack was at the point when the original double helix is in the process of unraveling. We also had a scheme to prevent our virus-gobbler happily eating every piece of DNA in the human body—an important detail, since your own DNA is in every cell of you.

  But our experiments, after a fine start, refused to follow the theory. We weren’t blaming anyone, but every evening we would look at each other and secretly wish that one of us were smart enough to decide what was going wrong.

  We were missing—what?

  When the class ended I went to the cafeteria in the basement, bought a carton of low-fat milk, and sat in the sun on a wooden bench just outside the side entrance of the building. I knew that once I was back in the lab I would be swept up in experimental detail; what I needed now was an idea.

  Oscar liked to describe things in mechanical terms. To him, we were making the smart little engine that could, the “Mean Machine” that would one day eat up any bad virus on Earth.

  I preferred a more biological analogy. Our new organism had “eyes,” chemical detectors sensitive to the presence of “unwinding proteins” that were present when DNA replication began. It had “hands,” enzymes that grabbed hold of the DNA as the double helix separated. There was “memory,” the template that defined the final required DNA composition. There were “muscles” in the form of abundant ATP—adenosine triphosphate, that provided the energy for nucleotides to be stripped off the sugar and phosphate bases of the DNA, and for other purine and pyrimidine molecules to replace them.

  And finally, there was reproduction. Our Mean Machine was self-replicating—and mortal. It would make copies to spread through every cell, but when it could no longer find DNA suitable for conversion it would die, quietly and with no effects on the host organism.

  If I had to point to one place as the soul of our device, it would be the memory template. That was a DNA molecule, or a set of them, and the DNA to be converted had to be close in form to the template, otherwise the energy needed for conversion would be too great. For example, we could never convert plant DNA to animal DNA, or animal to viral form. They were too different, and Oscar’s little engine that could, couldn’t.

  I squeezed the empty milk carton flat between my hands. How about this idea: we had used the most convenient source of animal DNA for our template, and made other DNA match it. Suppose the template itself had developed anomalies, and was foiling the match? We could find that out easily enough, with one of our new lab gadgets.

  I was standing up from the bench when someone moved in front of me. It was Susan Carter.

  “It’s not about my grade, Doctor Benilaide,” she said, before I could utter a word. “I know that’s all fixed and done with.”

  “You weren’t in my class this morning.”

  “I know. I’m sorry.” She waved a piece of paper in her right hand. “I had to get this. That’s why I want to talk to you. It’s about next year.”

  “What about next year?” I started uphill, and she fell into step
beside me.

  “Professor Sawyer told me you were taking graduate students. I wondered how to apply.” She thrust the piece of paper out in front of me. “That’s why I missed your lecture today, they told me if I wanted my grade transcript I had to get it this morning.”

  In bright sunlight my eyes seemed almost as good as ever. Surely I could hold off on spectacles for another year or two. I stared at the smudgy computer listing as we approached the biology lab and had quite a surprise: an isolated D, but mostly Cs, with three Bs and one A.

  “Susan, you did worse in my courses than anything else!”

  “I know. But they were the most interesting.”

  “And you did best in chemistry.”

  “Yes, but I don’t like chemistry. And Professor Sawyer told me that the more chemistry a biologist knows, the better. He says lots of biology teachers don’t know a thing.”

  Thank you, Hank Sawyer. I owed him something, but I was not sure what.

  “You think you can do better as a graduate student than as an undergraduate? It’s tougher.”

  “I hope I can. I’d sure try.”

  “Come in for a moment.” We had reached the door of the lab. “While you’re here, you can give me some of your skin and blood.”

  I laughed at her astonished expression. “Just to add to our tissue bank. We grab anyone who comes by here.” I walked inside. “Come on.”

  After a couple of timid trial stabs she pricked her thumb with a sterilized needle and squeezed half a dozen globules of dark-red blood onto the little plastic shield. While she did so I took a closer look at her grade transcript.

  “When are you leaving campus for the summer?”

  “The middle of next week. Liz Willis and I are driving west together, but she has five days of make-ups before she can go.”

  “Fine.” I carefully labeled the blood sample and put it in the refrigerated rack, along with similar ones from me, Oscar, and half the faculty. “Write a survey of the role of reverse transcriptase in RNA virus reproduction, and give it to me before you leave. Fifteen pages, no more. If it’s good I’ll see what I can do about next year.”

  “I’ll try to make sure it is.” She couldn’t keep the big grin off her face. “Thank you, Doctor Benilaide. I know I’ve given you some dumb answers in class, but I’ll make this report the best I can do.”

  We were walking back to the door. When we arrived there my body language ought to have told her that the meeting was over, but at the threshold she halted and turned to face me.

  “This is nothing to do with next year”—her eyes suddenly would not meet mine and her words came out in one embarrassed rush—“but I want to tell you how bad I feel about what Danny Fischer said this morning.”

  The young are marvelous. An older person would have at least given me the option of pretending that I hadn’t heard Danny Fischer’s words.

  “It was nothing. Just someone being a jerk.”

  “I told him that if I never see him again that’s too soon,” she continued. “And he’s dead wrong.” Her cheeks were flaming pink. “Liz and I think you’re very attractive. You could be married in a minute if you wanted to. People like you should be married.”

  “Thank you again.” I took her gently by the arm and steered her outside. “Don’t forget, I’ll need that paper by the middle of next week.”

  I closed the door and leaned against it. I didn’t know whether to laugh or cry. One thing was certain, if Susan Carter did research with me I was going to have my hands full. Your graduate students are like your children, you find you are involved in their health problems, love lives, hobbies, families, and diet, their job applications and their interviews, their hopes and their dreams. But I liked that. It was the closest to my own children that I was ever likely to get. Acute endometritis when I was twenty-six (thank the IUD) had left enough scar tissue that my gynecologist told me I was sterile “at the ninety-five percent probability level.” As she told me, that was in some ways worse than assured sterility. There was the depression of knowing you almost certainly could not have children, coupled with the worry that you might become pregnant.

  At the moment that was not a problem. The last love of my life had been almost two years ago. I went to look for Oscar, hidden away behind his racks. He and I never discussed such things as sex and children, but I judged him to be mildly heterosexual. Some day, almost without thinking about it, he would probably marry and become a kind, loving, and rather absentminded husband and father.

  “Any great thoughts?” Oscar had heard me coming, and was peering at me through a gap in a reagent rack.

  “The younger generation are clearly unfitted to run the world, but one day they’re going to do it anyway. No good ideas. How about you?”

  “Not an idea, exactly. But behold, I tell you a mystery.” He stood up and stepped delicately out from behind his desk, holding a listing. “Have you looked at the total amount of chemical energy that our little critter uses during the experiments?”

  “Not in detail. I know it’s too little for us to have changed replication in the way we’d like, and the comparison of initial and final DNA composition confirms that. It’s the same at the end as when it began.”

  “I know. But I just calculated how much energy we’d be using if every DNA base was being examined during the replication process, and there was no substitution going on. I get a result within a few percent of the energy the process is actually using.”

  “Telling us what?”

  “I’m not sure. Telling us that the experimental DNA is being compared with the template, at every nucleotide site—and then no changes are being made?” He handed me the listing. “Here’s the program, with my formulas for energy use built into it. Over to you, Alison. I have to go to another one of those godawful Interdepartmental Studies meetings. But I think there has to be something wrong with your experimental set-up.”

  Easy enough for Oscar to say, but I had checked the experiment over and over, to the point where if anything were wrong, I would probably be the last person on earth to see it.

  I took his listing. However, instead of going back to the experiment I went to my computer terminal. Thanks to Oscar’s passion for completeness, the entire data base for all our experiments was on-line, right back to the first run. He had arranged his new program to pull out the data for any single run and perform the energy calculation. But it was an easy change to add a program loop, so that Oscar’s calculation would be performed for every experiment in the data bank.

  While the computations were being executed I attached to my own directory in the Administration files and called up my grade assignments for the current semester. I had given Susan Carter a D. Now I changed it to a “To be assigned” category.

  Unfair to the other students? Probably. I was not going to worry about that. Show me a totally impartial teacher, and I’ll show you a robot.

  The results of Oscar’s program were buzzing out of the electrostatic printer, line by line. I went over to watch them. The computer was analyzing each experimental run in chronological order. The first page looked fine. The energy used was consistent with the desired DNA modification.

  The change appeared gradually, in the middle of the second page. A run appeared in which the ATP energy used was far too low—and it was also a failed experiment, in which the DNA “fingerprinting” showed that there had been no modification in the DNA sequence of our test material. The fingerprinting method was very precise, the same equipment and technique that was used routinely in forensic DNA work. Every individual in the world was different, and every one distinguishable, and the method’s reliability was the main reason that Oscar and I had decided to employ human DNA in our initial experiments. I found it hard to believe that we could be having trouble with the initial and final DNA matching.

  A couple of runs later, the same anomaly appeared again. And t
hen, as though the problem were itself infectious, the low energy use came more and more often. In the runs of the past thirty days, almost every energy use was too low, and no DNA modification seemed to be taking place in them.

  It had to be a problem with my experimental set-up. And yet I was sure it couldn’t be.

  When you have eliminated the impossible….

  After the results had been printed I set out to examine the sequence in more detail, particularly the place where the problem first seemed to appear.

  For no better reason than easy availability, I had used DNA from my own cells as the “template” for all our experiments. The DNA that we were trying to convert using our biological engine had been taken from a variety of individuals, and carefully stored in our “DNA library” in the form of tissue samples. Some people, such as Oscar, had provided samples more than once, and appeared in the DNA library several times. And it was that fact that finally offered some hint of a pattern.

  Two months ago, our experiments seemed to be working. And as long as we used DNA that had been in the library at least that long, the experiments worked still. But with samples that had been acquired more recently, the chance of a failed experiment increased. In the past three weeks only four runs had shown success, and two of them employed DNA that had been in the library for more than two months. The other two—I felt my skin begin to goose-pimple—were from visiting scientists, strangers who had stopped by the lab for a brief visit and been talked into giving us a little bit of blood and skin. The other samples in our library were from people that Oscar and I saw and worked with every day.

  I took a clean piece of paper and went back to my desk. By the time that Oscar reappeared carrying a pastrami sub sandwich and a giant Pepsi, I had the relevant facts pared down to a minimum and laid out as cleanly as I could. He read them aloud as he ate, holding the edges of the page with his greasy fingers.