Lessons Learned and the New Hampshire Police

My first moments at a Gordon Conference are permanently etched in my memory. I arrived at the Tilton School campus in Tilton, New Hampshire, in the late hours, about 11:00 p.m. I recall walking down dark stairs and suddenly finding myself in a bright room. It was extremely intimidating: I knew absolutely no one in the room; I was the only woman; and as the only graduate student, I was probably the youngest person attending the meeting by about ten years. Just as I was considering bolting back up the stairs like a lost Tilton high school student, one of the meeting organizers, Morton Bradbury, started talking to me about my science and made me feel incredibly welcome. As these few moments demonstrated, Gordon Conference participants are bound by science.

This was the 1984 Nuclear Proteins, Chromatin Structure, and Gene Regulation Conference, which had all the required elements of a Gordon Conference: cutting-edge science; endless hours of delightful speculation; discussion about a technique that was beaten to death (the footprint gel); a roommate (Sally Elgin); and finally, after the first or second late night in the bar, a stern sign that appeared by the pool prohibiting swimming after midnight.

I was fortunate to have been able to attend this GRC. My Ph.D. adviser, Tom Cech, could not attend and convinced speaker Joan Steitz to let me take his place in her session. Joan talked about small nuclear ribonucleoprotein particles (snRNPs) and, from what I remember, presented the first evidence that U4 and U6 (where U stands for uridine-rich) snRNPs were in the same complex. I talked about ribozymes–catalytic RNA molecules. At this meeting I also met the late Hal Weintraub, who was to become my postdoctoral mentor. Hal presented his current work on enhancers (to which proteins bind and thereby increase the rate of gene transcription)–mostly in the form of a chalk talk. He also talked about experiments being done in his lab by John Izant using antisense RNA, a strand complementary to an mRNA, to alter gene expression. I was already seeing from a “ribo-centric” perspective at this point in my life, so these experiments got my attention. John Burch, a postdoc in Hal’s lab, introduced me to Hal at the meeting, and a year later I began my postdoctoral work in Hal’s lab.

My goal was to understand why the antisense technique worked well in Xenopus oocytes but not in Xenopus embryos. As part of a control experiment I injected a double-stranded RNA (dsRNA) molecule into an embryo, which set the stage for what is still the focus of my research. When I compared the dsRNA before and after injection into the embryo, I discovered something perplexing: on a denaturing gel the RNA strands migrated the same way before and after incubation in the embryo, but on a native gel the RNA had an altered mobility.

In 1988, when I arrived at the Nucleic Acids GRC, which I was attending every year by that time, conference organizer Norm Pace asked if I would accept a last-minute invitation to speak. Of course I said yes. My observations of the dsRNA’s odd behavior captured the imagination of fellow attendees, and I remember the long hours of listening to everyone’s ideas about what had happened. With the ideas and input of my fellow scientists I finally figured out that the RNA was covalently modified: I had stumbled on an RNA editing enzyme now known as an ADAR (adenosine deaminase that acts on RNA).

I cochaired with Dick Gumport the memorable 1994 Nucleic Acids GRC. This was GRC’s last year using the New Hampton School site (in New Hampton, New Hampshire), which, although rustic, was beloved by the Nucleic Acids conferees; however, it was the conferees who helped put an end to GRC’s use of the site. I received a phone call only days before the meeting, informing me that we could not use the auditorium on Tuesday night because the headmaster had double-booked it. We were given other options, but in the end Dick and I decided to hold an afternoon rather than an evening session, thus violating the sanctity of reserving Gordon Conference afternoons for swimming, hiking, and discussing science. Further, the headmaster’s group was scheduled to use the auditorium at a precise time following our session. Although we did not vocalize it, both Dick and I knew our session would probably not finish on time. Never in our wildest dreams did we imagine such a dramatic outcome of running overtime.

My only explanation for what ensued is that scientists like drama. Because GRC had reserved the site far in advance, many attendees felt enormously slighted about being asked to vacate the auditorium. When our session did indeed run over, we heard whispers and rumblings outside the auditorium, and the conferees went into battle mode. The headmaster’s assistants started bringing me a disruptive stream of “warning notes” to end the session, instigating two disgruntled conferees, Dan Gottschling and Mark Roth, to barricade the doors. It was a surreal experience to be listening to elegant talks on structure with two conferees guarding the door like thugs. The headmaster continued to tug at the doors, and since the science was being compromised, I decided to attempt negotiation. I got up at the end of a talk, gave the secret handshake to the men guarding the doors, and left the auditorium to talk to . . . the New Hampton police! There I was, about to be arrested. I did not end the session immediately, but that was the end of New Hampton as a GRC site.

In 1997 another Gordon Conference came into my life–a conference devoted wholly to its namesake, RNA Editing, which began largely through the efforts of Harold Smith. Initially I was skeptical of a conference with such a narrow focus, but the meeting drew researchers from many other fields, and interest in the relationship of RNA editing to other fields grew. This was yet another lesson I learned from a Gordon Conference–this time without the police.