FAQ: Application Form
- General Application Questions
- Source of Cells
- Intended Research
- Additional Oversight
- Investigator Certification
- Dean Approval
- General Appendix Questions
- Appendix A
- Appendix B
- Appendix C
- Appendix D
- What is the rationale for the numbering system chosen for the ESCRO record #? For example, what does E007-001 mean?
- What is meant by “full,” “moderate,” and “minimal (administrative)” review and approval?
- When should I submit a new application?
- If my research will use differentiated progeny of hESCs and are no longer pluripotent, do I need to submit a new application?
- Why am I asked to provide rationale for using hESC lines?
- What type of information should I provide to justify the benefits of this research to society?
- Do you have an example of what type of information I should provide in the “Abstract”?
- What type of information do I need to provide to describe the “name of cell lines” and “source information”?
- Under “Source information,” do I need to include commercial sources from which I obtain somatic cells?
- What type of information do I need to provide to describe “location of storage and research”?
- What if I want to use derivatives from hESC lines or create genetically different cells from hESC lines (e.g. cardiomyocytes)?
- Why do I need to provide the blank consent of origin and IRB approval for lines that are not listed on the NIH hESC Registry?
- What is meant by “provenance is likely required”? What rationale is acceptable to ESCRO for requesting to waive provenance?
- What is a hESC-like line?
- What if my proposal requires IACUC and/or EH&S approval but I have not received an IACUC protocol # or EH&S protocol #?
- When do I need IRB approval?
- How do I know when the specimens I’ve received contain codes that are considered identifiable would require IRB review?
- Why am I asked about Office of Technology Transfer?
- Do all of the study personnel working on my hESC proposal take hESC training? If so, who is responsible for tracking this information and ensuring that they complete the training?
- What is the “annual survey” referenced in the 4th box of the Investigator Certification statements?
- What hESC research activities are considered prohibited?
- Why do I need to obtain my school Dean’s approval?
- What information should I provide regarding “origin of cells”?
- Why do I need to provide information regarding the origin of starting cells?
- Why do I have to justify the number of human embryos or oocytes I may use for my research proposal?
- Why am I asked to provide rationale for using certain genotypes?
- What type of information is sufficient to explain how to prevent chimeric animals from breeding?
- What type of information do I provide to justify the transplantation of hESCs into animals?
- What information do you want regarding the process that will be used?
- Why am I asked to provide scientific justification for generating human embryos from hESC or hESC-like lines? The cells came from human embryos of human tissue originally.
What is the rationale for the numbering system chosen for the ESCRO record #? For example, what does E007-001 mean?
Each researcher who submits a human embryonic stem cell (hESC) proposal for ESCRO approval will receive a unique researcher identification # (e.g. E007, E standing for ESCRO). That number will comprise the first half of every record number for all applications submitted by that researcher. The “001” portion of the example referenced above refers to the unique proposal that has been submitted by the researcher. For example, if Dr. Smith submits an application to study in vitro development of pre-existing anonymized hESC lines, the ESCRO record # would be E007 (representing Dr. Smith as PI) followed by 001 (representing the unique in vitro proposal) or E007-001. If Dr. Smith submits a second proposal, for example, one proposing to incorporate hESC lines into non-human animals, this new proposal would be E007 (representing Dr. Smith as PI) followed by 002 (representing the unique chimerism proposal) or E007-002. A third application would be numbered E007-003, and so forth.
What is meant by “full,” “moderate,” and “minimal (administrative)” review and approval?
When full ESCRO review and approval have occurred, the full convened ESCRO Committee has reviewed and approved your proposal. Categories of research that may require full ESCRO review are described in section V.D.2 of GIM 36. ESCRO meets once each month to review hESC proposals.
When administrative ESCRO review occurs, the ESCRO office and ESCRO Chair have reviewed and approved your proposal. Categories of research that may require minimal ESCRO review are described in section V.D.3 of GIM 36. The anticipated turnaround time from submission date to final ESCRO approval date is less than the time required for full review items. The ESCRO Chair will determine when moderate ESCRO review is needed.
Moderate review will involve 3 subcommittee reviewers in addition to the ESCRO Chair review. Although GIM 36 does not specifically describe what categories of research may require moderate review, this type of review is left to the discretion of the ESCRO Chair.
Please contact the ESCRO Office at firstname.lastname@example.org or at 206-685-7010 with any questions.
If my research will use differentiated progeny of hESCs and are no longer pluripotent, do I need to submit a new application?
ESCRO does not require further review and approval of your hESC research if you have established that the differentiated hESCs are no longer pluripotent. For example, your previous ESCRO application involved inducing the differentiation of hESCs and you have now grown the cells over many passages using media conditions that ensure the loss of pluripotency. These growth conditions are published and are widely accepted by the scientific community as demonstrating that pluripotency of the hESCs no longer exists. Finally, you have shown that your differentiated hESCs no longer express pluripotency markers but rather express markers of a differentiated cell type. If these criteria are met, your research with these cells no longer requires ESCRO review and approval.
If you are no longer working with the original pluripotent hESC lines, please work with the ESCRO office to close your existing ESCRO application.
Why am I asked to provide rationale for using hESC lines?
One charge of ESCRO is to gain public trust. The application asks for rationale so that PIs provide information to address potential public concern. The information below should be included in your response:
- Explain why other approaches have weaknesses and how your proposed method avoids or mitigates against these problems. For example, one response might be that hESCs are much less likely to be mutated.
- Describe the advantages/disadvantages of using hESC for this project compared to other types of cells, for example, adult stem cells.
- Cite and describe supporting data and research in peer-reviewed scientific journals. If there are valid alternatives to using hESC to answer research questions, please briefly describe why these alternatives are not being used.
What type of information should I provide to justify the benefits of this research to society?
Describe how the potential benefits should outweigh the potential impacts and risks. Explain how the research is intended to advance science and medical knowledge and/or benefit human health.
Do you have an example of what type of information I should provide in the “Abstract”?
Below is an excerpt of an ideal Abstract description:
Abstract: (describe in 250 words or less, in layman’s terms, the goals of the research, rationale for using hESC lines, brief description of the approach, and benefits to society)
Goals: To assess the efficacy of newly generated hESC lines by investigating the fate of hES cells that were 1) injected into various sites within the adult mouse, to test their ability to generate teratomas, e.g., sub-cutaneous, intramuscular, kidney capsules and testes, or 2) injected into a mouse embryo to generate xeno-chimeras, to test their normal development up to mouse embryonic day 11.5.
Rationale & Benefit: Teratoma formation is the only assay we currently have to assess the array of tissues that can be formed from a particular hESC line. Given that these tissues are tumors, growth is disorganized and difficult to relate to normal development. Contribution to chimeras provides a context to the development. If a cell is present within a particular tissue, development is considered normal and the starting hESC lines would be thought to have the capability of forming that tissue. hESC lines have different abilities following directed in vitro differentiation. There are as many protocols for directed differentiation as there are investigators and target tissues. Development within the in vivo context of a chimera could potentially allow us to assess the ability of any particular line more accurately than either in vitro assays or teratoma formation. We will start this project using non-human primate ES cell lines, with the plan that if the primate-cell assays work well, and once ESCRO approval is given, we will proceed to assess all human ES cell lines in this fashion.
Methods: Direct injection of undifferentiated and differentiated hESCs and iPSCs into tissues in question.
What type of information do I need to provide to describe the “name of cell lines” and “source information”?
The source is the collaborator. If you received a line from a colleague at UCSF, identify that contact person by providing his/her name and institution. If you received the line from an investigator within the Institute of Stem Cell and Regenerative Medicine (ISCRM) community, reference the UW colleague as a source.
For cell lines that are listed on the NIH Human Embryonic Stem Cell Registry, an example of name of cell lines and source information would be:
H7, National Stem Cell Bank, or
UC06 (HSF6), University of California, San Francisco via Susan L. Fisher.
For lines not listed on the NIH Human Embryonic Stem Cell Registry, an example of name of cell lines and source information would be:
HUES-2 Harvard University via Elena Kfoury
Under “Source information,” do I need to include commercial sources from which I obtain somatic cells?
ESCRO does not review the use of somatic cells unless the investigator plans to induce pluripotency and manipulate the hESC-like line further in vivo, in which case provenance documentation is needed. Therefore, with this one exception, the ESCRO application does not require you to list sources of somatic cells.
What type of information do I need to provide to describe “location of storage and research”?
Give the UW building name and room number. For each room, explain whether you plan to conduct tissue-culture work, wet-bench work, surgery, microscopy, etc. This information will help other oversight offices, such as IACUC or EH&S, evaluate your application as well.
Examples of research and storage information would be:
HSB J229 -80oC freezer storage
HSB J229C microscopy
HSB J229A tissue culture
HSB J234 wet-bench work
For work conducted off-site, give the complete address, for example:
960 Republican Street
Seattle, WA 98109
as well as room and use information.
What if I want to use derivatives from hESC lines or create genetically different cells from hESC lines (e.g. cardiomyocytes)?
Yes, if the hESC-derived cell line still retains the ability to create all three embryonic germ layers. According to section V.D. of GIM 36, “Except as provided in section V. E. below, all hESC research, including research involving the use or creation of a hESC-derived cell line, must be reviewed and approved by the ESCRO Committee prior to the commencement of the research.” An hESC-derived line means, “one or more cells or cell line, including a hESC line created from the destruction of a human embryo, but does not include a hESC line created by SCNT without destruction of a human embryo.”
For example, modifying the H7 cell line by addition of a GFP-reporter would create a genetically distinct hESC-derived cell line that still retains the characteristics of an embryonic stem cell; use of this new cell line would require ESCRO approval.
No, if the hESC derivative no longer retains the ability to generate all three embryonic germ layers. A hESC derivative is defined as “any DNA, RNA, protein, or other biological products secreted by or extracted from a hESC, including an adult stem cell, but does not include any HESC line, HESC-derived cell line, data, or intellectual property.”
Consent and IRB documents should ensure that individual decisions about donation will not affect the quality of care the donor receives and should ensure that donations are made free from undue influence. Please include original donor consent forms in original language as well as English translation for:
- egg donations made in context of research;
- egg donations made in the context of fertility treatment;
- sperm donor consent form for research;
- sperm donor consent form made in context of fertility treatment, consent form from donor of blastocyst if different from above;
- somatic cell donor consent form.
GIM 36 prohibits payment to a donor solely for the purpose of creating a human embryo to be used in hESC research.
What is meant by “provenance is likely required”? What rationale is acceptable to ESCRO for requesting to waive provenance?
In general, provenance documentation is required for any non-federally approved hESC-line(s). An exception to this requirement may include when induced pluripotent stem cell lines are created from anonymized somatic cell sources where the PI cannot ascertain the identity of the individual who donated the somatic cell. In such cases, the PI should briefly explain the history of the cell line and cite relevant literature supporting the origin of the cell line.
What is a hESC-like line?
A cell that can generate all three embryonic germ layers. Embryonic stem cells or “ESC” are defined in GIM 36 as “an undifferentiated, pluripotent stem cell, typically derived from an embryo.” Cells that resemble ESCs but were induced by transformation with specific genes or drugs are pluripotent. Since induced pluripotent cells act like stem cells but were not derived from embryos, they are called “hESC-like”.
What if my proposal requires IACUC and/or EH&S approval but I have not received an IACUC protocol # or EH&S protocol #?
ESCRO review will occur concurrently with other Oversight Office reviews. If you have submitted an application to another Oversight Office but have not received an Oversight Office protocol # yet for that application, please email the ESCRO office (email@example.com) with the following information:
- Title of the application applicable to the hESC research
- Oversight Office that the application was submitted to
- Date of submission
Although the ESCRO office will work as much as possible with existing Oversight Offices to obtain protocol # information and approval information, some of the Oversight Offices cannot issue final approval until they receive confirmation of ESCRO review and approval. For example, if your proposal involves EH&S and/or IACUC, they cannot issue final approval until ESCRO has approved your protocol.
When do I need IRB approval?
IRB review is required when the research involves human subjects. Human subjects can be people, human specimens (such as embryos), or data in which the subject’s identity is known or can be readily ascertained. Examples of human subjects research include:
- Interactions with living individuals, such as discussions with potential gamete donors. These interactions include the transplantation of human cells or test articles, such as differentiated cells derived from human embryos or human fetal tissue, into human recipients;
- Clinical research involving use of cells or test articles regulated by the Food and Drug Administration, such as drugs, devices, and biological products;
- Human cell lines where the donor(s) may be identified, including cells that retain links (such as a code).
If sponsors require verification that the research is not human subjects research, PIs must at the very least complete a Human Subject’s Division (HSD) form called the “Biological Specimens Determination” form. This form allows the HSD to make a formal determination that the project is not research involving human subjects. The Biological Specimens Determination Form is documentation that the researcher can then use for his or her funding source, regulatory bodies, etc.
How do I know when the specimens I’ve received contain codes that are considered identifiable would require IRB review?
Coded specimens may be considered identifiable and IRB review is required when you, the sponsor, or any other person involved in your study:
- Have any identifying information about the individuals from whom the specimens were obtained;
- Will or could acquire identifying information about the individuals from whom the specimens were obtained;
- Could acquire access to a code key or other information that links the specimens to the individuals from whom they were obtained;
- Could acquire identifying information about the specimen donors through a constellation of variables accompanying the specimens, such as an unusual pedigree describing a rare disease;
If you have questions about IRB review, please contact Arna Elezovic, Human Subjects Division, at 206-543-0098 or firstname.lastname@example.org.
Why am I asked about Office of Technology Transfer?
ESCRO is attempting to serve as an information clearinghouse for Oversight Offices that may require that you submit an application. Office of Technology Transfer is listed in the table to merely serve as a prompt to remind you to consider contacting them in the event that any specimens or materials may be exchanged between you and collaborators.
Do all of the study personnel working on my hESC proposal take hESC training? If so, who is responsible for tracking this information and ensuring that they complete the training?
ESCRO requires that the PI of the hESC research proposal track and ensure that all of their study personnel are appropriately trained in hESC methods, ethics, and fiscal training. The required hESC training is still under development. Once this program is developed and released for use, the ESCRO office will establish appropriate tracking procedures.
ESCRO will rely on the PI to determine which study personnel are sufficiently involved in hESC research to warrant ongoing compliance training. For example, a junior investigator working 50% on a hESC project and a senior scientist with a small but critical role, such as evaluating hESC pluripotency, would both require training. Someone whose only job is labeling the tubes would not.
What is the “annual survey” referenced in the 4th box of the Investigator Certification statements?
The ESCRO office will send the PI a list of hESC lines that she/he reported previously as being used in your lab. In addition, the list will show those personnel (by employee ID only) that were reported on the financial supplement will also be listed. The ESCRO office would appreciate report of any changes in these items. For example, if you derive cell lines, please report what you have named those lines. ESCRO is required to maintain a registry of all hESC lines in use at the University of Washington. ESCRO is required to track personnel working on research involving non-federally approved lines to comply with GIM 36 regarding allocation of salary monies.
What hESC research activities are considered prohibited?
Please review GIM 36, Section V(C) for a listing of prohibited research. If you have any questions as to whether these activities pertain to your research, please contact email@example.com.
Why do I need to obtain my school Dean’s approval?
The Dean of your school is responsible for reviewing how resources are allocated and what facilities and equipment are used.
What information should I provide regarding “origin of cells”?
Explain how the lines were derived. Examples could include: by SCNT, by destruction of embryos at a fertility clinic, or by inducing pluripotency of a specific type of somatic cell (name the type of cell).
Why do I need to provide information regarding the origin of starting cells?
ESCRO is charged with maintaining a database of information regarding the origin, function, and handling of hESCs at the University of Washington. Please provide the basis for the selection of donors (inclusion and exclusion criteria) and rationale for conducting research with particular genotypes. Such justification helps ensure that vulnerable populations are not enlisted for research without scientific justification and without the promise that these populations will benefit from research in the future. Please comment on how you anticipate donor populations might someday benefit from the research, if applicable.
Why do I have to justify the number of human embryos or oocytes I may use for my research proposal?
We ask for justification because we recognize that scientists are the legitimate stewards of these resources and the public trust depends on demonstrating judicious use of human oocytes, embryonic, or fetal tissues.
Why am I asked to provide rationale for using certain genotypes?
Such justification helps ensure that vulnerable populations are not enlisted for research without scientific justification and without the promise that these populations will benefit from research in the future. Please specify how you plan to assure the confidentiality and anonymity of donors.
What type of information is sufficient to explain how to prevent chimeric animals from breeding?
Maintenance of animals in separate cages would ensure an inability to breed. Furthermore, GIM 36 stipulates that any animal that receives human cells is autoclaved or incinerated following the study.
What type of information do I provide to justify the transplantation of hESCs into animals?
If there is a reasonable possibility that, after transplantation of hESCs, the animal will exhibit human-like traits (appearance, cognitive, or behavioral), discuss the procedures that will be implemented for management, documentation and reporting of such occurrences to IACUC and ESCRO.
As a reminder, GIM 36 prohibits the following:
- Implanting a chimeric embryo containing non-human cells, including ESCs, into the uterus of a human;
- Implanting a chimeric embryo containing hESCs into a uterus of a nonhuman primate and allowing the resulting pregnancy to progress to the point of independent viability;
- Breeding of a chimeric animal having hESCs that were introduced during any stage of the animal’s embryonic or fetal development;
- Breeding of a chimerical animal having hESCs where there is a reasonable possibility that human genetic material could be incorporated into the animal’s germ cells.
In addition, ESCRO has determined that certain categories of induced, pluripotent stem-cell research (iPSC research) require ESCRO review and approval. These categories include the following:
- Transplantation of iPSCs into research animals;
- Transplantation of iPSCs into humans;
- Use of iPSCs to create an embryo.
What information do you want regarding the process that will be used?
Please explain what measures you are taking to minimize toxicity and ensure safe transplantation into humans. As a reminder, if your research involves transplantation of hESC line(s) or hESC-like line(s) into humans, IRB review is required.
Why am I asked to provide scientific justification for generating human embryos from hESC or hESC-like lines? The cells came from human embryos of human tissue originally.
Creating embryos specifically for research purposes raises many ethical concerns with the public. In addition, such embryos must also be destroyed by day 12 of development. Some would argue that scientists are playing God, creating a life only to destroy it.