Center for Science in Society

Bridging Stem Cell Research and Political Science

Metisse Zahler

Project Description

On May 16, 2006, I joined the lab of Dr. Meri Firpo at the Stem Cell Institute at the University of Minnesota. In being part of this lab, I will be studying stem cells and their development and relationship to diabetes. This research will continue for the remainder of the summer, ending in August. I will be putting in an average of 25 hours a week in the lab, and doing additional individual research on political culture and structures dealing with the national and international controversies surrounding stem cell research. Also, in association with the Institute, I will be participating in Journal clubs and presentations on Wednesday and Friday afternoons with fellow lab researchers, technicians, etc. I hope to eventually be able to use what I learn over the summer in the lab and the surrounding political arena to shape a senior thesis topic on the political culture and structure of stem cell research in the international perspective.

Under the supervision of Dr. Firpo, I will be investigating the expression stability of genes introduced into human embryonic stem cells that are useful for isolating beta cell precursors at various stages. This will be done by working to identify the factors which regulate the development of human pancreatic beta (insulin-producing) cells from human embryonic stem cells, in order to yield an in vitro model of human development and as a source of cells for treating type 1 Diabetes. In the lab I will be making preparations of recombinant plasmid vectors to be introduced into the cells, as well as assisting the laboratory in introducing these vectors into bacteria and human embryonic stem cells. Preparation of plasmid vectors requires making large bacteria cultures. The plasmids contain genes encoding fluorescent proteins, which will be subsequently used to monitor expression stability.

I will update the Center for Science in Society periodically with what I have learned in my research and from participating in the lab. At the end of the summer, I will write a short paper reporting what I learned, if it was what was expected, how I can relate it on a larger scale to politics, society, and science, and other social concerns regarding the project and my findings.

Week of May 15

This week was my introduction/training at the Stem Cell Institute at the University of Minnesota. The Institute is an incredibly interesting place filled with truly interesting people of all ages and nationalities. In the lab I am working in, under the supervision of Dr. Meri Firpo, there are two other girls (University of Minnesota soon-to-be Seniors), a lab technician, and one other summer student from the University of Wisconsin.

For my training and getting accustomed to the lab (and institute), I had to take a number of lab safety and security lessons and quizzes, get cleared for security, and got to know the people in my lab. I observed many of the procedures: PCRs, Gel Electrophorisis, and other common day-to-day procedures. Also, I was taught what exactly stem cells are, how they are obtained, procedures involving them, and how to identify them. In addition I was taught how to grow the cells and how to clean the solution they are in, among other things.

Week of May 22

This week, finally cleared for security and safety, I was able to begin working (hands on) in the lab. Due to my lack of experience and minimal lab knowledge, I have been assigned to many tasks, which will help me in getting to know the lab, supplies, and procedures. I have been assigned to two tasks in particular; first, I have been working to create a data base of all supplies in the lab including all biochemistry and tissue culture antibodies, solutions, etc. My other task is to go through the lab's -80 degree freezer and catalog the cells and solutions, etc, that have been harvested and created as far back as 1997. I have learned so much so far and am really enjoying it!

In addition I have learned to create gel electrophorisis plates so as to run gels. Also I have observed ODs (so I can perform them), Digestions, and more. Eventually as the summer progresses, I will be, in addition to the above, cleaning cell cultures and even harvesting and growing feeder cells (which come from mouse embryos).

Outside of the lab, I attend lab meetings every Monday afternoon in which we discuss projects in the lab, problems, accomplishments, needs, etc. On Wednesday afternoons the Institute has conferences with presentations given by members of other labs, or even outside researchers. This week we had a speaker from Milan, Italy discussing stem cells in association with muscular dystrophy, with exclusive tests performed on dogs (and incredible results too). Friday afternoons we have journal club, in which one person from the Institute picks a journal article and we all read it before that afternoon. Then, we all come together and discuss the paper.

I am more than enjoying this experience and am excited for the rest of the summer! The people are wonderful and the research is incredible. Paired with my individual research on the political cultures of stem cell research (outside of the lab), I can't wait to begin writing my thesis, it is going to be a lot of fun and very rewarding. In terms of my individual research, I have found a great deal of information and have been working hard to organize it! I have also contacted a Professor at Berkeley who teaches a class entitled, "the language and politics of stem cell research and cloning." I am still waiting to hear back from her with any advice for my thesis research.

Week of May 30, 2006

This week I was very busy running numerous biochemistry procedures including digestions, purifications, and mini preps. All of this is in preparation for DNA insertion into the embryonic stem cells, a process called nuclearporation. A lecture this week was on the engineering views/procedures in adult stem cells, mainly with the use of mice.

I am starting to feel much more comfortable in my position in the lab, getting a real "groove" in learning the procedures and performing them. On my own, individually, I am still awaiting a response from the UC Berkeley Professor I had contacted. Also, I have doing large scale searches on scientific journal engines and creating a database of sorts of information for myself.

Week of June 5, 2006

This week I continued doing biochemistry procedures on my own, without supervision, performing mini-preps of DNA and growing bacteria to produce DNA for eventual nuclearporation of DNA into the human embryonic cells. I also learned some new procedures in the tissue culture lab, such as cleaning the media of the embryonic stem cells, as well as how to look at the cells and interpret their growth, colony size, etc. In terms of lectures, there was only one this week and it was on the engineering aspects of growing embryonic cells.

Most of the work in the lab went slow this week due to much needed data analysis and trying to find what DNA was needed for the nuclearporation and how to digest it so as to have correct cuts (with the correct restrictive enzymes), etc. Also, we are waiting for a new derivation procedure (of our PI Dr. Firpo), for the human embryonic stem cells, to be approved by the NIH. In addition to lab work, I learned about karyotyping the ES cells and performed mega preps (large scale preparations of bacteria, in which the DNA is harvested for digestions and then purified and used to be put into the cells).

Independently, I have talked to many people in the lab about their opinions and views of working with human embryonic stem cells and outside political views. Many of them referred me to a new book entitled, "Stem Cell Now: From the Experiment That Shook the World to the New Politics of Life" by Christopher Thomas Scott. Daniel Levine, a Biotechnology Reporter from the San Francisco Business Times writes of the book,

""Stem Cell Now" is a rare primer that deftly provides a layman with a highly readable grounding in the science, moral controversy and political dimensions of stem cells. Christopher Scott has an unusual perspective to bring to the subject as someone trained as a molecular biologist, but who also served as a business consultant and journalist. Scott was not only an assistant vice chancellor of research at the University of California at San Francisco, but also a founder of the short-lived and highly acclaimed "Acumen Journal of Science." As such, he plays comfortably in the intersection of science, business and society. Scott waits until the end of the book to offer his own positions on the issues of stem cell research, but his point in writing the book is that any discussion about the broader social issues should be grounded in the science. To that end, this is a welcome contribution to informing the discussion and a surprisingly breezy read for anyone who wants to understand the promise, the limitations and the controversy surrounding stem cells." I am very excited to read this book and share what is discussed in it. However, when I ordered it, I was surprised to find that it is back-ordered until August. Other independent research, I am still waiting to hear from the Professor at Berkeley and I am also reading an interesting article published in 2005 from the Financial Times and Scientific American Magazines.

Week of June 12, 2006

This week has been very interesting and busy! I am now doing large-scale procedures fully on my own with no supervision what so ever. I am interpreting all of my own data and giving full reports to my supervisor without aid in needing to understand things! I completed a project on a certain DNA, which was used to nuclearporate the stem cells and have already begun another project. I am working with two different structures, creating DNA, from bacteria cultures of them, and studying how they can be cut with specific enzymes.

I learned this week how difficult and frustrating science can be as well! In one process I made a single, small mistake and it ruined my entire project! So, I had to start from the beginning. Also, in a mega prep I performed with large stocks of bacteria, I produced DNA. This was very frustrating because this one process takes 18 hours to grow the bacteria, then another full day in lab to purify and harvest the DNA. So, next week I will have to create new stocks of DNA and perform the entire process again. It is not uncommon to not collect DNA from this procedure, but it is frustrating. But, I will continue on and learn from any and all mistakes I have or will make!

Great news this week was that our new derivation procedure was approved by the NIH and will begin to be used in the lab.

Everything in the lab is still up to my expectations, even exceeding them! I am learning so much and doing so much. I wish it were as fast paced with my individual research on the politics of stem cells. I have so much information, but I just need to sort through it and begin to organize it. I have more or less given up on the Professor from Berkeley, but will try and contact her one last time. I continue to read the Scientific American/Financial Times article and am learning so much from it. This summer is so rewarding!

Lastly, I have learned that I will be helping to teach a training course in July on how to work with ES cells. This is very exciting and something I look forward to doing. Week of June 19: This week in lab I continued with mega preps and mini-preps in preparing DNA for nuclearporation. My first trial of the week resulted in no DNA, but the other trials were successful and I produced a large amount of DNA, which was very exciting! Lab work was similar to past weeks, but I did accomplish quite a lot in my independent research this week. I investigated something called the BioBank in the United Kingdom, which began earlier this year (Spring 2007). It does not have anything to do with Stem cells directly, but it is a large, long-term study in the United Kingdom intended to investigate the role of genetic predisposition and environmental exposure (including nutrition, lifestyle, medications etc.) to the development of disease. The study plans to follow about 500,000 individuals (whom all have volunteered their participation), in the UK aged 40-69. Initial enrollment will take place over a 5-year span, with the volunteers being followed for 25 years thereafter. The participants are invited to visit an assessment center, where they complete an automated questionnaire and are interviewed regarding lifestyle, medical history, and nutritional habits; basic variables such weight, height, blood pressure etc. are measured; and blood and urine samples are taken. These samples are preserved so that it will possible to later extract DNA and measure other biologically important substances. During the whole duration of the study, all disease events, drug prescriptions, and deaths of the participants are recorded in a database, taking advantage of the centralized UK National Health Service. If medical problems are detected during the initial physical, the participant's physician is notified. Problems detected later, such as genetic risk factors, are not to be communicated to the participant (which could be viewed as a potentially controversial point). Once the data collection has begun, researchers can apply to use the database. A typical study would compare a sample of participants who developed a particular disease, such as cancer, heart disease, diabetes or Alzheimer's disease, with a sample of those that did not, in an attempt to measure the benefits, risk contribution, and interaction of specific genes, lifestyles, and medications.

Overall it is a very interesting project and a large one at that! Funded by the UK Department of Health, the Medical Research Council, the Scottish Executive, and the Wellcome Trust medical research charity, this project, like the study of stem cells, has a great impact on the political and science spectrums. It will be very interesting to follow it alongside stem cell political cultures.

Weeks of July 10 and 17

I want to start by saying that the last 2 weeks were difficult to write individually on due to their slow pace and extreme difficulties with experiments. The week on July 10, I continued to run tests with the plasmid I have been working on; linearizing it, performing diagnostic digestions, mini-preps, and running gels. However, after each test I failed to have the results I was looking for. This continued for the rest of the week. In addition to these tests, I had been working hard on preparing for an NIH sponsored training course my lab and the other embryonic stem cell lab would be teaching together. The course is the hESC Training Program: Essentials of Human Embryonic Stem Cell Culture Techniques. Our run of the course was set to be a 3-day training course, providing hands-on training in the culture of human embryonic stem cells (hESC). Participants would be offered written training materials, laboratory instruction and practice, as well as lectures from experts in the field on stem cell research and clinical applications. The course is set to run on the 18-20 of July.

In political news regarding stem cells, there is much going on here, in the United States as all research institutes set-up for the proposed veto of the stem cell bill by President Bush, next week. By vetoing this bill, only stem cell lines found/created before 2001 will be able to be used, which will be a great disadvantage for medical findings.

The week of July 17 was extremely busy! I continued with the tests I had been running on my plasmid, but finally, after over 3 weeks of failing results, found that the plasmid can't be right! As a result it looks as though we will have to have it sequenced (to find out exactly what it is), as well as possibly having to re-clone the plasmid. Nonetheless, this means that my work with this plasmid is done and so I will finally move onward with other research!

This week I was finally also introduced into tissue culture and was given my own batch of mouse fibroblasts (what we use to grow the ES cells on) to thaw and plate. My first batch looked really good with no contamination and healthy growth. However, because the cells were never really meant to go further than a test run (to make sure I knew what I was doing!), they were discarded after a few days. We began the hES cell course on Tuesday and over the few days of the course we acquired new fibroblasts, which were them passed on to me to grow. On Thursday, I split the cells (when they are confluent-or grow heavily on the plate they need to be slit up into smaller quantities of cells on more plates) and on Sunday I came in to split the cells again. I am at a second passaging so far and the cells seem quite healthy and have yet to get any contamination (and I hope to keep them that way!).

The course went more or less well. There were a few glitches, but the students seemed to learn a lot, as did I! I was able to get an in-depth look at the growth and maintenance of the hES cells (things I don't personally do on my own in the lab) and was also able to sit in on the lectures, which were really interesting as well!

There was a lot of research to be done this week on my independent research in the political cultures of stem cell research. Back in April 2004, 206 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported. In May 2005, the House of Representatives voted 238-194 to loosen the limitations on federally funded embryonic stem-cell research by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors, despite Bush's promise to veto the bill if passed. On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill, 63-37, which would have made it legal for the Federal government to spend Federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures and this past week, on July 19, 2006 President Bush vetoed this bill. The second bill passed by senate makes it illegal to create, grow, and abort fetuses for research purposes, and the third bill would encourage stem cell research using cells from sources other than embryos, e.g., adult and umbilical stem cells, in an effort to cure diseases and treat injuries. At this point in time, the National Institutes of Health has 399 funding opportunities for researchers interested in hES cells. In 2005 the NIH funded $607 million worth of stem cell research, of which, $39 million was specifically used for hES cells. Of the 514 currently recruiting clinical trials that are using stem cells as treatment, the federal government is supporting 206 of them; however, none of these trials are using hES cells.

Final weeks

The last few weeks at the Stem Cell Institute really came together filled with finishing up projects and organizing everything I began so that another member of the lab could take over after I left. As for my cells, my first batch grew beautifully, but after a second splitting, they stopped growing and remained in an odd flower-like shape. As a result they had to be discarded. My second batch of cells were very sparse at the beginning. I let them grow a little longer that usual so as to be confluent enough for a successful split, and when I did decided to split them, they disappeared! It was hard to pin-point what may have happened. For starters, we had mass contamination throughout the lab. But, I think my cells survived it! There are many procedure-based steps, which may have killed the cells also. But regardless, I have learned a strong base of what it takes to grow strong, healthy feeder cells.

The rest of the last few weeks/days of my time in the lab were spent wrapping up the work I had been doing (primary work done in the lab), on the Rainbow Project. This included making preparations of recombinant plasmid vectors to be introduced into the cells, as well as assisting the laboratory in introducing these vectors into bacteria and human embryonic stem cells. Preparation of the plasmid vectors required making large bacteria cultures (mega preps). The plasmids contained gene encoding fluorescent proteins, which are subsequently used to monitor expression stability. Since this was my primary project in the lab, the whole last week in the lab was spent putting together all my findings, making sure all samples and DNA created was labeled properly and measured accurately.

In my own research, I finished collecting all my data (for the most part). However, a lot of time was spent catching up and collecting the many sources regarding the veto and public/political rebuttal or comments/feedback. I exchanged contacts (email) with journalists/researchers at Time magazine. Also, I created my own database of all sources and international divisions of my research. So, I have a collection of European articles/research journals, divided by country, date, and subject content (embryonic stem cells, public opinion, governmental actions, views of international research spectrum, etc). Also, I have several books, journals, and personal contacts made over this summer in regard to the political controversies of stem cell research.

The experiences I had this summer both in and out of the lab were incredible and more than rewarding. The people I met, the work I was able to do and observe, and the research I did on my own created a major ground base for my thesis and well as my personal/academic interests in the subject.