A Month of Meetings
Authors: Fintan R. Steele
Journal: Molecular Therapy (2000)

As daylight hours grow shorter in the northern hemisphere, the list of meetings relevant to gene therapy grows longer. The past 2 months saw the formation of the Latin American Society of Gene Therapy, the annual Gene Therapy camping trip to Cold Spring Harbor, the usual large gathering of the American Society of Human Genetics, and the 8th Annual Meeting of the European Society of Gene Therapy. Even the most hardened meeting fanatic may be excused for feeling that “enough is enough.” Nevertheless, this constellation of meetings provides an interesting glimpse not only of the science that continues to advance, but also of the current preoccupations of all parties involved in gene therapy. The following is an attempt to summarize them, less from the point of view of science, perhaps, but from what the undertones of the past 2 months of meetings reveal about the field. The usual disclaimer applies: these are purely the opinions of the author, not of the Editorial Board of Molecular Therapy. I also hesitate to mention specific papers/posters I found interesting, lest such either be interpreted as a disinterest in other presentations or be taken as a sure bet for acceptance for publication. Several hundred Latin American researchers gathered in Guadalajara, Mexico, on September 8th and 9th for the “1er Simposium Internacional de Terapia Génica en México,” although the meeting ultimately became the First Annual Meeting of the Latin American Society of Gene Therapy (ALTG). Estuardo Aguilar-Cordova, recently of Baylor but now at Harvard, was announced as the first president of ALTG. Although only 14 presentations in total, the small number of talks was more than met by the enthusiasm of the participants. Several invited U.S. speakers (including Doug Jolly of Chiron, Dale Ando of Cell Genesys, John Nemunaitis of U.S. Oncology, and Laura Aguilar of Harvard) gave talks, in addition to several Latin American research presentations. Included in the Latin American talks were updates on clinical trials in prostate cancer (Augusto Rojas), advances in cervical cancer gene therapy (Jaime Berumen Campos), and the large-scale preparation of clinical grade viral vectors (Fernando Siller López). In addition, Juan Armendáriz Borunda, the organizer of the meeting, presented exciting data on the reversion of cirrhosis using uPA gene therapy in an animal model (Molecular Therapy, in press). Despite significant resource scarcity, the rigor of the science that could be done under tough conditions was impressive and argues for increased support, perhaps in the form of collaborations, with Latin American laboratories. The meeting was also colored by the keen interest of the participants in ethical and regulatory issues. Gerald McKenny of Rice University reviewed the relevant international ethical guidelines, and a great deal of discussion about ethical issues specific to Latin American showed the concern of participants that such be addressed and quickly. However, regulatory issues gathered most of the attention. Indeed, it appears that the impetus for the formation of ALTG is the awareness that Latin American countries will play a critical role in future gene therapy clinical trials, but that the current state of regulatory confusion within and between countries needs to be addressed first by a unified front of researchers. The necessity for this was underlined in a talk by Hugh Barrera Saldaña, who recounted the labyrinthine path followed to obtain approval of one trial in one country alone. Although presented in a humorous manner, the bureaucratic terror over having to regulate new things unleashed in a torrent of official letters was a bit, well, unfunny. It is hoped that ALGT will help prevent future such episodes and that a common regulatory code can be adopted throughout Latin America. To this end, there was much interest among the participants about the current state of regulatory issues surrounding gene therapy in the United States. The sense is that many of the hurdles here may be unnecessarily high (and getting higher) and that ALTG is in the unique position to build more streamlined and attainable guidelines from scratch without sacrificing patient safety or ethical issues. It will be interesting to see how the nascent Society addresses these issues as it continues to grow. Cold Spring Harbor Laboratory is known for great meetings, in addition to its surfeit of DNA sculptures and excellent scientific research. However, despite the best efforts of the four organizers (Jeff Leiden of Abbott Labs nee Harvard, Gary Nabel of NIH nee Michigan, Margaret Liu nee Chiron, and Jim Wilson, University of Pennsylvania), the Cold Spring Harbor Meeting on Gene Therapy (September 25–29, 2000) somehow lacked both the excitement and breadth of attendance of past meetings. This is not a criticism of attendees: after all, I was admitted to the meeting! Indeed, it is far more likely that the attendance problems and the range of new science presented reflected the fact that there are, well, too many gene therapy meetings. (Some may also argue that there are too many gene therapy journals as well. I agree, although we may disagree over which ones are superfluous). As one participant in the European Society of Gene Therapy (ESGT) meeting (below) said, “Given the choice of camping at Cold Spring Harbor or walking the streets of Stockholm, it's a no-brainer.” Despite early attendance problems requiring the extension of the abstract submission date, the organizers brought together several interesting and provocative talks and posters in all areas of molecular therapy. Particularly strong sessions, at least from my point of view, were those on “Immunity and Gene Transfer,” an area of renewed research interest following the adverse event in the OTC trial last year, and on “New Technology, Stem Cells and Tissue Engineering.” In fact, none of the sessions was really disappointing, and the poster sessions, as usual, hinted at big things to come. However, there was no denying the lack of excitement or “electricity” that has characterized CSHL gene therapy meetings in the past, and there were notable absences or highly limited attendance on the part of many leaders in the field. One of the most striking moments of the meeting came during a panel discussion on “Clinical Trial Design, Data Safety Monitoring, and Bioethics,” chaired by Phil Reilly. Kathy Zoon, director of CBER at FDA, pointed out that, in the past year, investigational new drug (IND) applications for gene therapy protocols submitted to CBER dropped from 55 last year to 26 this year. This is clearly not part of the normal variation seen over the past 10 years. Furthermore, gene therapy IND amendments received this year so far have almost reached 1500, nearly a doubling of the previous year. What does the decreased number of IND applications mean? There is no question that the events of the past year are in some way behind this decrease. Does this mean that fewer scientists are willing to pursue gene therapy for fear of scientific and/or public relations disaster? I think not, particularly given the excitement evident at other meetings. Rather, it suggests that institutions, both private and academic, are taking stock of their commitments to such work in light of both growing public concern and increasing regulatory burden. Indeed, this interpretation is born out by the large simultaneous increase in amendments to existing INDs. Although some may think that this is a long-overdue correction to a too-optimistic and too-ambitious clinical gene therapy push in the past, others fear this is the beginning of an overcorrective knee-jerk response that may ultimately bring true gene therapy progress to a halt. The truth is undoubtedly somewhere in between, although this precipitous decrease in IND applications suggests that the prophets of doom may have a point. Regarding the number of meetings: Perhaps the Keystone conference on gene therapy (January) and Cold Spring Harbor (fall) could work out a way to alternate years? With the annual ASGT and ESGT meetings, in addition to the constellation of more focussed, smaller meetings, this may help both maintain their respective reputations for small, top-flight gatherings of cutting-edge science. The usual cast of thousands attended the 50th Annual Meeting of the American Society of Human Genetics (ASHG) in Philadelphia, Pennsylvania, from October 3 to 7, 2000. ASHG is truly a genetic feast: One can lose oneself in the intricacies of population genetics algorithms all the way to bioinformatic meta-analyses. Gene therapy applications, however, were scarce, and those that were present were limited largely to one slide session on “Therapy of Genetic Disorders,” chaired by Brendan Lee of Baylor and Savio Woo of Mount Sinai, in the middle of the meeting. Further, most of the seven talks in this session were on pharmacological treatment of genetic disorders. In all fairness, it is true that gene therapy is not a primary focus of the ASHG meeting. Nevertheless, it is also true that gene therapy has become even less of a presence at ASHG over the past several years. Particularly telling this year is the lack of gene therapy studies (indeed, the words “gene therapy” are not even used) in ASHG's 45-page Press Program Reference Book: A Guide to Clinical Highlights of the Scientific Program Specially Designed for Members of the Press. The sole study mentioned, listed under “Correction of Inherited Defects,” summarizes studies by Jeff Chamberlain (University of Michigan) and his colleagues on a mouse model of DMD, and this was presented in a session on “Gene Structure and Function” rather than “Therapy of Genetic Disorders.” Intentional or not, the ASHG steered clear of any possible press on the subject of gene therapy. Given ASHG's formidable press relationship savvy, I tend to think this was a conscious decision. Apart from an understandable shyness about press on gene therapy, it is surprising that at a time when there are glimmers of success (e.g., recent work in cardiovascular, hematopoietic, blood clotting, and autoimmune diseases) that these were not more emphasized at a genetics society meeting. Perhaps a partial reason for this can be found in the ASHG Board's April 2000 Statement on Gene Therapy. In it, the Board states that “Both the lack of progress [in gene therapy] and the safety issues are related to a poorly developed scientific base when experimentation began and to an initial lack of appreciation for the extensive experimental work in gene delivery and gene expression that would be required prior to clinical studies.” The Board does say that the field has “begun to mature,” but the statement comes down strongly on the side of basic research before proceeding. Though not surprising, the report highlights once again the inherent tension of between clinical and bench science that most gene therapy researchers and regulatory agencies face in moving from one to the other. The ASHG Board proposes a “litmus test” for all those involved before proceeding to clinical gene therapy trial: “If you or your family were in this circumstance, would you enroll yourself or your loved one in this trial?” While this litmus test might work to prevent the worst and promote the best trials, it does little to guide decisions in the gray area in which the majority of trials will take place. It is difficult enough for two scientists to agree, much less a whole group of regulatory authorities, ethicists, physicians, and family members. Despite the somewhat chilly atmosphere of ASHG toward gene therapy, it would be good to see more representation of the field at this annual meeting. Although undeniably a “large” meeting, interactions with expert ASHG members in genomics, etc., could be fertile ground for breeding new ideas about therapeutic approaches. It also may help basic genetic researchers see that their labors can bear fruit in unexpected and gratifying new ways. Similar to the ALTG meeting, although with a significant edge in scientific resources, the 8th Meeting of the European Society of Gene Therapy (ESGT) in Stockholm, Sweden, from October 7 to 10 was buoyed up by excitement and confidence in the future of gene therapy. With an attendance of more than 600, the meeting had an impressive array of invited speakers in addition to presentations and posters attesting to the healthy state of gene therapy in Europe and beyond. Special lectures by Judah Folkman of Harvard University (“A Role for Angiogenic and Antiangiogenic Gene Therapy”), Kathy High from Children's Hospital in Philadelphia (“AAV-Mediated Gene Therapy for Hemophilia B”), and Robert Gallo of the Institute for Human Virology (“Need for New Approaches to HIV/AIDS Therapy”) framed a busy 3-day program that featured surprising and gratifying amounts of new data and progress. Of the 24 oral presentation sessions scheduled (many concurrent with one or two others), those that appeared to draw the largest crowds were five sessions given over to discussions of the ethics or regulatory aspects of gene therapy. Granted, such sessions have always been a part of gene therapy meetings, but I cannot recall any meeting where there was such emphasis and where such sessions were so heavily integrated into the total program. Although it is likely that the sad events of the past year in the United States helped spark the increased interest, it is clear that the ESGT is taking these issues seriously in their own right. Given the excitement and quality of the meeting, it is puzzling why the ESGT membership numbers remain so low (less than 300). Indeed, the ASGT has about as many European members as the ESGT itself. This is certainly not due to lack of effort on the part of outgoing president Olivier Danos and members of the Board. Recent alignment with the Japanese Society of Gene Therapy, along with continued growth of the field itself in Europe and beyond, should help address this problem. One final note: the setting (Stockholm) was amazing. Besides being a beautiful city, the closing ceremony and dinner in City Hall, site of the awards dinner and dance for Nobel Prize winners, were awe-inspiring. Indeed, the year 2000 winners in Physiology or Medicine were announced the day of the closing dinner! As this is as close to winning a Nobel as many of us will get—although there is always hope—it was particularly enjoyable. It will be interesting to see if next year's ESGT venue (Turkey) can provide as great a draw and as good a meeting. All four of these meetings were, as would be expected, colored in some way by the adverse events of the past year here in the United States. Gene therapy as a field is mired in the need to address regulatory and ethical issues on several fronts, and it may be some time before these are sorted out. Thus, it is no surprise that all four of these meetings paid increased intention to these issues to varying degrees, whether as an aside (ASHG making its “Statement” available) or directly and completely (ESGT's coordinated series of presentations). Most importantly, the meetings attest to the health of gene therapy research and even to the enthusiasm that still exists despite a year of bad press and very public scrutiny. Even if there are too many meetings, it is gratifying that there are enough researchers still interested in pushing the field forward to attend them and enough new data coming out to warrant them.