Genetic Engineering of Human Embryos- for discussion

Commentary by Ernst-Martin Füchtbauer

The new and accelerating technical development of the CRISPR/Cas9 system opens up for the possibility of targeted genetic modifications in germline competent human embryos. This is an avenue, which until very recently has been regarded as absolutely off limits. To cross the border between genetic modifications of somatic cells and germline cells was simply not conceivable, at least in most Western countries. Indeed, the border has not yet been crossed, but we are getting closer.

In two recent papers Chinese scientists used triploid human embryos as a ‘model’ to either treat ß-thalassemia [1] or to recapitulate a spontaneous mutation in the CCR5 gene [2], which results in resistance against HIV infections. Both targets are clearly chosen due to their potential for future therapeutic application.

Shortly after the first of the two papers was published, the Board of Directors of the ISTT posted a statement [3], which among other arguments contains the following sentence:

Uses of genetic engineering in human embryos should be limited to disease mitigation for those diseases where no other option is available; we reject the idea of “designer babies”.

This raises the question whether there are at all diseases where there are no other options (now or in the future). Hereditary diseases are rarely transmitted by homozygous parents, which makes preimplantation diagnostics (PID) an obvious safer and ethically far less disputed alternative. The example, ß-thalassemia reaches in very limited populations, like the Maldives, a frequency that puts about 1% of couples at risk to be double homozygous. But still, is not a CRISPR/Cas9 based hematopoietic stem cell therapy the obvious and much easier developed therapy?

However, the case of targeting CCR5 is fundamentally different. As no one can claim that being wild type for CCR5 is a disease, this is a clear designer approach. Given that we know relatively little about the function of CCR5, one might wonder how we can be sure that it is beneficial to mutate it in a world of ever changing microbial threats. It seems that developing a CCR5 blocking drug or somatic mutations of CCR5 in HIV patients is the obvious way forward.

It is my feeling that many colleagues, some of whom I greatly admire, are beginning to accept experiments with the obvious goal to modify the human germline ‘if it is the only cure for severe diseases’. However, I have not heard one convincing example of such disease that is not in principle “treatable” or “avoidable”. Finally we should keep in mind that the Hardy-Weinberg equation ridicules all eugenic attempts to clean the population from ‘disease’ alleles.

I am increasingly concerned because the discussion in our community has, within a few months, taken an almost purely technical turn about off target risks and efficiency. We neglect many decades of thorough philosophical and ethical literature on the issue. There is more at stake than the possible treatment of a few rare diseases.

These questions are too important to just wait and see. We as ISTT members are so close to the topic that we need to have an honest and open discussion about our opinions. This blog could be a starting point and I invite/encourage you to add to this discussion.

[1] Liang, P. et al. Protein Cell (2015) http://dx.doi.org/10.1007/s13238-015-0153-5

[2] Kang, X. et al. J. Assist. Reprod. Genet. (2016) http://link.springer.com/article/10.1007%2Fs10815-016-0710-8

[3] http://www.montonerin.es/isttlegacy/isttblog/?p=1581

Newly elected 2016 ISTT Board of Directors members

ISTT BOD electees

Branko Zevnik Lynn Doglio Peter Hohenstein

The official results of the recent election for the ISTT Board of Directors are in, and we congratulate Branko Zevnik, Lynn Doglio and Peter Hohenstein on their election to the ISTT Board. Branko Zevnik (Cologne, Germany) is the head of the in vivo Research Facility at the University of Cologne. Lynn Doglio (Chicago, USA) is the Director of the Transgenic and Targeted Mutagenesis Laboratory at Northwestern University. Peter Hohenstein (Edinburgh, United Kingdom) is a Group Leader and Chair of the Small Animal Facility Management Committee at The Roslin Institute. All three candidates received the support of the majority of voting ISTT members. While they will start their three-year terms at TT2016 to be held in Prague, Czech Republic, they will be immediately appointed as Board members-elect. This will allow them to interact with the rest of the ISTT Board members and become familiar with the administration and management of the ISTT. Congratulations to all of them!

In addition, the ISTT would like to express its respect and sincere appreciation for the commitment and participation of all the candidates who were involved in the ISTT election process. As well, we would like to thank Tom Fielder, Wojtek Auerbach, and Boris Jerchow for their service on the ISTT Council and Board of Directors. These three Board members have contributed greatly to the management of the ISTT (and will continue to do so until TT2016). It is due in large part to the contributions of our members that we have the vibrant Society that we do.

ISTT Registration Awards for TT2016 meeting in Prague

ISTT Registration Awards for TT2016 meeting in Prague
ISTT Registration Awards for TT2016 meeting in Prague

A minimum of six Registration Awards will be sponsored by the International Society for Transgenic Technologies for ISTT members wishing to attend the 13th Transgenic Technologies (TT2016) meeting in Prague, The Czech Republic, on 20-23rd March, 2016. Selected applicants will be awarded funding to cover registration fees plus attendance at all social events. However, the award does not cover travel expenses, hotel accommodation or attendance at pre-meeting events.

Applicants who are not yet members of the ISTT may join the ISTT and simultaneously submit their Registration Award application. Only those applications from members who have paid their current annual fees will be considered.

Procedure
Applicants must register first at the TT2016 Meeting website and select, as a payment method, “Application for Registration Awards” as a payment method. The ISTT will pay the Registration Fee of all applicants selected for an award. Applicants not selected will be kindly requested to pay the corresponding registration fee.
Applications and additional required documents (see below) should be sent, along with the meeting registration confirmation, to the official ISTT email address, istt@transtechsociety.org, by 30th November, 2015.

Additional Documentation Required
a) Applicant’s CV
b) For ordinary members, a letter from the applicant describing how he/she will benefit from attending the TT meeting
c) For technician/student members, a letter of support from the applicant’s PI or supervisor stating how attendance will benefit the applicant’s career

Selection Process
ISTT Registration awards will be selected by a subset of ISTT Council members, with preference given to:
1) Student/Technician ISTT Members
2) ISTT Members submitting an abstract for presentation as a poster/short-oral communication at the TT meeting
3) Any other ISTT Member

Decision
Awards to the selected applicants will be announced by December 15th, 2015 and awardees will receive a diploma marking the event at the end of the TT2016 Meeting.

ISTT Board of Directors: STATEMENT ON GENETIC ENGINEERING OF HUMAN EMBRYOS

ISTT Board of Directors

STATEMENT ON GENETIC ENGINEERING OF HUMAN EMBRYOS

June 10, 2015

Genetic engineering in animals is a process that has engendered great excitement as well as great anxiety. The technology is used to study developmental processes (using small animals such as the mouse, zebra fish, fruit fly, worm, etc.), determine gene function, and mimic human and animal disease processes. Perhaps the greatest promises of this technology are to develop and test drugs and to perform gene therapy, both of which are intended to prevent or cure disease.

Until recently, a variety of limitations made the technology impractical for all but a few species of animals (primarily mice). However, with the advent of new gene-editing systems, where components are inexpensive, readily generated in the laboratory, and applicable to virtually any species, it is now feasible to perform genetic engineering in the human embryo. Changes made in an embryo brought to term would no longer be confined to that individual, but could be passed through the germline to affect future generations.

A recent publication [Liang, P. et al. Protein Cellhttp://dx.doi.org/10.1007/s13238-015-0153-5 (2015)] brought this reality squarely into the public consciousness. In this study, the CRISPR/Cas9 system was used to edit the genome of human embryos. To their credit, the authors were careful to use only non-viable embryos. Furthermore, their detailed examination of the engineered embryos revealed both the intended and unintended modifications that resulted. This study clearly demonstrates that the CRISPR/Cas9 system is currently too imprecise and inefficient for genetic engineering of human embryos for implantation, gestation and birth.

Members of the ISTT use CRISPR/Cas9 technology, as well as other gene-editing technologies, routinely. Many of our members have had integral roles in the development of these technologies and therefore recognize the power of these systems. It is with that knowledge and foresight that the ISTT Board of Directors issues this statement (while understanding that more nuanced discussions and decisions will be needed as the technology improves):

  • Genetic engineering technology, in its current state, is error-prone and must not be used in human embryos intended for implantation.
  • Studies to test new genetic engineering technology in human embryos should be postponed until proven completely safe and effective in other species.
  • New methods of genetic engineering must be carefully assessed to ensure that risk to the human population is negligible.
  • Uses of genetic engineering in human embryos should be limited to disease mitigation for those diseases where no other option is available; we reject the idea of “designer babies.”
  • We strongly urge worldwide agreement on minimum standards for gene editing experiments in human embryos, and will promote such measures with our members. Until such standards have been established, we remain opposed to making any genetic alterations in human embryos that could be inherited by future generations.

 

The 2014 ISTT Election Process

The 2014 ISTT Election Process
The 2014 ISTT Election Process

The 2014 ISTT Election Process has been launched. All members of the International Society for Transgenic Technologies are warmly invited to elect the next ISTT President, ISTT Secretary, ISTT Treasurer and three new board members. All these new positions at the ISTT Board will begin their term of service on January 1st, 2015. The 2014 ISTT elections will take place within the members-only area of the ISTT web site, during the entire month of June 2014. Results will be published shortly thereafter. The ISTT wishes to express its deepest gratitude and sincere acknowledgement to all 12 nominated candidates which will run for the various positions to be elected within the board. The official nominated candidates participating in this 2014 ISTT Election Process are: Jan Parker-Thornburg (USA), Lynn Doglio (USA), Channabasavaiah B Gurumurthy (USA), Aimee Stablewski (USA), Cheryl Bock (USA), Martina Crispo (Uruguay), Larry Johnson (USA), Sagrario Ortega (Spain), Xin Rairdan (USA), Tanya Templeton (Australia), Elizabeth Williams (Australia) and Branko Zevnik (Germany). All candidates deserve our most sincere appreciation for their generous willingness to serve and further contribute to the success of our Society. Good luck to everyone!

Requesting proposals to host the 13th Transgenic Technology (TT2016) meeting

Requesting proposals to host the 13th Transgenic Technology (TT2016) meeting
Requesting proposals to host the 13th Transgenic Technology (TT2016) meeting

Dear ISTT members,

We are pleased to invite your proposals for hosting the 13th Transgenic Technology Meeting (TT2016) in February-March 2016. The updated ISTT bylaws, which were approved at the TT2013 meeting in China, now allow proposals to be received from anywhere in the world, without the requirement for a rotation between regions. Therefore, ISTT members from all continents are encouraged to consider hosting the TT2016 meeting in their city, with the support of their institution(s).

Please note that only ISTT members are entitled to submit proposals to host a TT meeting.

Important points to be addressed in any submitted proposal:

  1. The proposal must have the support of the hosting institution(s). Letters of support from the corresponding director(s) of organizing institution(s) must be provided.
  2. The hosting institution(s) are fully liable for the organization of the meeting, including all economic aspects.
  3. A proposed preliminary budget should be included in the proposal, along with suggested registration fees.
  4. A preliminary program for the TT2016 meeting, including topics (not necessarily speakers) and proposed workshops should be provided. This program should take into account the topics and speakers invited at previous TT meetings, avoiding unnecessary repetition. Full information regarding previous TT meetings organized is available at the members-only area, within the “meetings” tab.
  5. Proposed venue and dates for the TT2016 should be indicated. Exact sites and dates might be subjected to change later, if required, after obtaining the approval from the ISTT council. Information regarding the venue and/or the city where the TT2016 meeting would take place is always desirable as is proof that the venue will be available at the scheduled dates.
  6. Proposed committees should be presented, which should include at a minimum: Organizing Committee, Scientific Advisory Committee.
  7. A meeting Chair (who must be ISTT member) should be clearly identified.
  8. Since TT meetings are the most important activity of the ISTT, the President and other members of the ISTT Council have to be involved in committees and collaborate with local organizers in defining the final program.
  9. Upon selection, a contract will have to be signed between the hosting institution(s) and the ISTT
  10. Information regarding suggested accommodation facilities (and prices) for participants should be provided.
  11. The expected organization of a hands-on workshop on a selected topic, to take place immediately before or after the meeting, is always desirable.
  12. The involvement of a professional meeting organizer is desirable but not essential if there are viable alternatives, such as institutional meeting support staff.
  13. Information on accessibility of the city from international airports as well as between the conference venue and accommodation should be provided. A list of hotels close to the conference including price range is desirable.
  14. Finally, an outline of the proposed social activities should be included.

We look forward to receiving interesting proposals from all over the world. Please submit your proposal (ideally all information organized into a single PDF document) to istt@transtechsociety.org by Friday 27 June 2014. The evaluation committee might contact any proponent in order to request any additional/missing information that would be required to better assess the proposal. The selected venue will be announced by September 30, 2014, and the Chair of the selected proposal will be kindly invited to introduce the highlights of the TT2016 meeting at the closing ceremony of the TT2014 meeting in Edinburgh.

Thanks for your due consideration of this message,

Boris Jerchow
Jorge Sztein
Karen Brennan

ISTT Council sub-committee
in charge of evaluating TT2016 proposals

ISTT Registration Awards for the TT2014 meeting in Edinburgh, Scotland, UK, 6-8 October 2014

ISTT Registration Awards for the TT2014 meeting in Edinburgh, Scotland, UK, 6-8 October 2014
ISTT Registration Awards for the TT2014 meeting in Edinburgh, Scotland, UK, 6-8 October 2014

A minimum of six Registration Awards will be sponsored by the International Society for Transgenic Technologies for ISTT members wishing to attend the 12th Transgenic Technologies (TT2014) meeting in Edinburgh, Scotland, UK, on 6-8 October 2014. Selected applicants will be awarded funding to cover registration fees plus attendance at all social events. However, the award does not cover travel expenses, hotel accommodation or attendance at pre-meeting events.

Applicants who are not yet members of the ISTT may join the ISTT and simultaneously submit their Registration Award application. Only those applications from members who have paid their current (2014) annual fees will be considered.

Procedure:

Applicants must first register for the TT2014 meeting and select, as a payment method, “Application for Registration Awards.” The ISTT will send the registration fee of those selected directly to the TT2014 meeting organizer.

Applications and additional required documents (see below) should be sent, along with the meeting registration confirmation, to the official ISTT email address, istt@transtechsociety.org, by June 30, 2014.

Additional documentation required:
a) Applicant’s CV
b) For ordinary members, a letter from the applicant describing how he/she will benefit from attending the TT meeting
c) For technician/student members, a letter of support from the applicant’s PI or supervisor stating how attendance will benefit the applicant’s career.

Selection Process:
Registration Awards will be selected by a subset of ISTT Council members, with preference given to:
1) Student/Technician ISTT Members
2) ISTT Members submitting an abstract for presentation as a poster/short-oral communication at the TT meeting
3) Any other ISTT Member

Decision:
Awards to six selected applicants will be announced by July 15, 2014 and awardees will receive a diploma marking the event at the end of the TT2014 Meeting.

The ISTT wishes you Merry Christmas and a Happy New Year!

The ISTT wishes you Merry Christmas and a Happy New Year!
The ISTT wishes you Merry Christmas and a Happy New Year!

The International Society for Transgenic Technologies (ISTT) wishes you all Merry Christmas and a Happy New Year!. The already traditional ISTT Christmas Postcard has been conceived this year by Elizabeth Williams (TASQ, Brisbane, Queensland, Australia), who managed to engage the rest of ISTT council members to contribute with Christmas scenes taken from the places where they live or work, threfore providing all of us with the nice opportunity to grasp how the Christmas season is perceived and how cities are decorated in several countries around the world. All the 34 Christmas pictures shown here have been captured directly and kindly shared by ISTT council members, as follows: Brisbane-Australia (by Elizabeth Williams), Sydney-Australia (by Karen Brennan), Colmar-France (by Benoît Kanzler), Ridgewood-NJ-USA (by Wojtek Auerbach), Madrid-Spain (by Lluis Montoliu), Lexington-KY-USA (by Carlisle Landel), Irvine-CA-USA (by Tom Fielder), Salamanca-Spain (by Manuel Sanchez-Martin), Pasadena-CA-USA (by Shirley Pease), Berlin-Germany (by Boris Jerchow), Buffalo-NY-USA (by Aimee Stablewski), Ann Arbor-MI-USA (by Thom Saunders). Hope you all enjoy them!. Merry Christmas and Happy New Year!

ISTT Best Poster Awards at TT meetings sponsored by Charles River

ISTT Best Poster Awards at TT meetings sponsored by Charles River
ISTT Best Poster Awards at TT meetings sponsored by Charles River

The International Society for Transgenic Technologies (ISTT), in collaboration with Charles River Laboratories International, Inc. (CRL), has establised the ISTT BEST POSTER AWARDS that will be given at the Transgenic Technology (TT) Meetings. The ISTT Best Poster Awards recognize outstanding work presented by participants at Transgenic Technology (TT) meetings. The ISTT Best Poster Awards are generously sponsored by Charles River Laboratories International, Inc. (CRL).

All posters accepted and presented at a TT meeting will be eligible for these ISTT Best Poster Awards. An ISTT Best Poster Awards committee will be established by the ISTT in order to select the awarded posters among among all presented communications submitted to a TT meeting as Posters. This committee might include members of the ISTT Council, members of the Local Organizing Committee and any other willing ISTT member and will have a Chair. The ISTT Council will nominate the members of this Committee and its Chair. The number of Posters to be awarded might vary, from TT meeting to TT meeting, although the figure of selecting the three best posters presented might be used as a reference. The scientific and technical quality of the Poster, he novelty of the results presented, as well as the artwork applied and the overall layout of the Poster will be judged by this Committee, among any additional criteria, at its sole discretion. The ISTT will define the nature of the presents to be given to the presenters of the selected awarded Posters.

The next TT meeting where the ISTT Poster Awards will be given is the 12th Transgenic Technology meeting, TT2014, to be held on 6-8 October 2014 in Ediburgh, Scotland, UK.

Workshop report: animals bred, but not used in experiments

Workshop:  “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)
Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands.

Experiments in biomedical science use large numbers of laboratory animals. It is a fact that to provide these animals, regularly more animals are bred than are finally used in the experiments planned. The Ministry of Economic Affairs as the competent body of the Netherlands had asked Prof. Coenraad Hendriksen and Dr. Jan-Bas Prins to organize a workshop to identify the reasons for the breeding of surplus animals and to devise recommendations as to how the number of animals that are bred but not used can be reduced to a minimum.

A number of experts from different fields of laboratory animal science were invited for a two day workshop to the Hotel Duin & Kruidberg in Santpoort, a town close to Amsterdam, to discuss these issues and to develop a paper for the Dutch authorities. Obviously, many of the laboratory animals bred are genetically altered (GA) animals. Moreover, techniques to cryopreserve GA animal lines could be a means to reduce the number of animals that are bred. The invitation was therefore extended to the ISTT to send a representative to take part in this workshop.

Here, I will give a short summary of the topics that have been discussed and of the outcomes. However, I refer you to the final report of the workshop, parts of which have been developed within individual small workgroups and will be put together into a final document by the kind efforts of Coenraad and Jan-Bas. I will inform you immediately upon the publication of this report.

A topic central to the discussion was the identification of reasons for the production of animals that are then not used in experiments. A major reason for this is the production of unwanted sexes and unwanted genotypes. The participants agreed that good planning can considerably reduce the number of surplus animals. At the same time, resources can be saved and either used for additional experiments or for cost reduction. However, breeding schemes with multiple alleles, as well as the organization of a facility, can be complex. A strong need for counseling as well as education of users of laboratory animals was identified, to make them competent to plan accordingly. The centralization of the breeding colonies under the responsibility of the facility management was discussed as a possibility to streamline breeding strategies. On the other hand, for the time being, this does not seem to be feasible for very many facilities. Local Animal Welfare Committees should evaluate local SOPs and develop a catalogue of best practices to help keep surplus animals to a minimum. GA animal lines should be cryopreserved immediately after their creation when there is no need to breed extra animals for this purpose and when animals from test rederivations can be used for experiments or for the breeding colony. Thereby, the lines are protected from disaster and from genetic drift at the same time, live mice can be terminated at any time, and the lines can be easily shipped to collaborators. Lines should be made available to collaborators as early as possibly to avoid generating the same line at different places. In case expertise for cryopreservation is lacking, lines can be donated to repositories like EMMA where they are cryopreserved free of charge. Investigators should always consider sharing lines with the scientific community through such repositories.

A second important topic discussed during the workshop was the use of new technologies for the generation of GA animals as well as for their experimental analysis. New lines should be directly generated on the desired background. In case backcrossing is needed, speed congenic strategies should be used to reduce the number of animals needed during that process. Technologies utilizing the targeting of nucleases to the locus of interest (ZFNs, TALENs, CRISPER/Cas9) promise to eventually allow the generation of GA lines with reduced numbers of animals directly on the desired background. Complex strategies for the generation of customized animals for specific experiments were presented. It was agreed that these should be freely available. However, individual scientists and institutes should evaluate whether it is worth adopting a new and complicated technique. Since the process of setting up complex protocols may well lead to the use of high numbers of animals, investigators should consider collaborating with colleagues who perform similar experiments at large scales.

Ethical considerations let us come to the understanding that there is an intrinsic value of life. We found that it is for this reason that it is morally wrong to kill more animals than absolutely necessary. Biomedical science is tasked with producing answers to pressing questions on the molecular functions of life and disease and finding new cures. It was pointed out that the principles of the 3R’s have to be respected at all times, but a number of animal experiments are indispensable. In this context, it is unavoidable to breed animals that are not used for these experiments, but it is important to ensure that their numbers are kept to a minimum.

Boris Jerchow
Member of ISTT’s Executive Council
October 23, 2013

List of participants and affiliations, excluding those who were unable to send permission for disclosure:

van der Broek, Frank, NVWA, The Netherlands; Aleström, Peter, The Norwegian Zebrafish Platform, Norway; Benavides, Fernando, University of Texas, USA*; Bussell, James, Wellcom Trust Sanger Institute, UK*; Chrobot, Nichola, MRC Harwell, UK; van Es, Johan, Hubrecht University, The Netherlands; Fentener van Vlissingen, Martje, Erasmus MC, The Netherlands; Hendriksen, Coenraad, InTraVacc, The Netherlands; Hohenstein, Peter, Roslin Intitute, UK*; Krimpenfort, Paul, NKI, The Netherlands; Morton, David, UK; Prins, Jan-Bas, LUMC, The Netherlands; Raspa, Marcello, EMMA, Italy*; Tramper, Ronno, Consultant, The Netherlands; van der Valk, Jan, NKCA; Wilbertz, Johannes, Karolinska Institutet, Sweden*; Ohl, Frauke, Utrecht University, The Netherlands; Pool, Chris, KNAW, The Netherlands; Witler, Lars, Max-Planck Institute Mol. Gen., Berlin, Germany*.

* ISTT members

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)
Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)