Alison Scheidler

Final Seminar Paper

May 17, 2002

Embryonic Stem Cell Research – A Balancing Approach

Introduction

Today’s Legislatures are continually confronted with debates concerning the bio-life sciences such as cloning or stem cell research.[1]  These controversial areas of research are very similar in their underlying debates though each does have its own variations on the arguments for or against developing the technology.[2]  United States legislatures implemented human embryonic stem cell (ESC) regulations just this past year[3] and have since faced several other bills regarding stem cell research along with a growing number of legislation concerning other bio-life science research.  Presently, the United States Senate is debating competing bills to ban cloning either entirely or to allow therapeutic cloning for use with stem cell technology.[4]  Though the scope of this paper is restricted to analyzing the development of ESC regulations the theory behind the balancing approach advocated herein is applicable to the development of regulations in the other bio-life science research areas as well. 

The new ESC regulations announced August 9, 2001 were created in response to increasing pressure from the National Institute of Health (NIH)[5], scientific researchers, the medical community, and the public at large.[6]  These regulations allow federal funding for human embryonic stem cell (hESC) research conducted on approved human embryonic stem cell lines.[7]  Following the announcement, the NIH published the ESC Registry listing seventy-two approved stem cell lines.[8]

This Note will propose that the present regulations on ESC research are too restrictive and that they were developed with too great of a focus on public morality.  This Note will propose that appropriate ESC regulations should be determined using a balancing approach that weighs multiple factors.  The factors suggested in this Note include the effect the regulations will have on our country’s economy, health, leadership positions both scientifically and morally, and public morals encompassing both sides of the issue.  In applying this balancing theory, this Note concludes that the United States should loosely regulate embryonic stem cell research, imposing less restrictions at this early stage in the development of stem cell research. 

First, this note will set forth a basic embryonic stem cell overview disclosing the development in this area of research and the basic underlying science.  Next this note will present the development of regulations in the United States for ESC research and describe the present regulations now in effect.  Third, this note will examine the factors that should be used in determining how ESC research should be regulated.  Finally, this note will conclude with a proposed ESC regulation system that will reduce the present restrictions on ESC research.

I.              Background

A.  Stem Cells – The Basics

Cells are the basic building blocks of life.[9]  Some cells survive on their own while other cells have evolved into complex organisms.[10]  The average human body is composed of about a thousand million million cells.[11]  Within complex organisms like human beings cells are organized into tissues, the tissues into organs, and the organs grouped together by common function into systems which act in a coordinated manner to maintain an entire organism.[12]  There are over 200 types of cells in the human body.[13]  These cells are organized into four types of tissues: muscle, nervous, epithelial, and connective tissues.[14]  The logical question that follows is, what makes these cells so different from one another that they form the four completely separate and distinct tissues of the human body?[15]  The answer lies in the mysterious DNA housed in the nucleus of the cell. 

Every somatic cell in the body contains the genetic material or DNA for the entire organism.[16]  It is estimated that the genetic material contained in the nucleus of a single cell would stretch to be about two meters in length.[17]  With that amount of information stored in the cell’s microscopic nucleus, cells have had to evolve efficient means of getting to the information they need and quickly passing over unnecessary information.[18] 

Imagine for a moment a library filled with all the books in the world.  Now imagine that the library had to fit in one small building.  One method to conserve space would be to place the books on movable rows of shelves and place the shelves directly adjacent to one another only sliding the shelves apart when someone had to reach a book shelved between the two rows.  Now imagine the difference if the librarian knew that the only books the library’s users would want to look at were biology text books, then the librarian could make access to these books easier by pushing together all the rows of books in the other subject areas while leaving openings between the rows containing biology texts.  Instead of constantly having to move the rows for its users, the library would be easily accessible for use day in and day out while still containing all the other books within its walls. 

This is essentially the approach the nucleus of the cell takes for storing and using its genetic information, only instead of a librarian determining which rows of books to leave open, cellular signal direct the cell as to which DNA to leave accessible.  These cellular signals occur during the developmental process and result in the cell’s differentiation.[19]  A cell is differentiated when it has developed into a specific type of cell such as a nerve, muscle, or tissue cell.[20]  Differentiation occurs after a cell’s nucleus has been imprinted so certain portions of its DNA are tightly wrapped making it inaccessible thereby allowing the cell to more efficiently locate the DNA it needs to perform its designated function in the organism.[21]  DNA directs the cell much like a computer program directs a computer.[22]  The nucleic acids that compose the DNA are arranged into gene sequences.[23]  These genes code for specific proteins that a cell will produce.[24]  Genes interact with one another and with the environment in determining the features of a phenotype.[25] 

Although the different types of cells in the body perform different functions and therefore use different genes or different portions of their DNA meaning that different portions of the DNA are left open in the nucleus for the cell to read, all of the cells derive from the same origin, the totipotent cells of the human embryo.[26]  A totipotent cell has the ability to form any type of cell found in the human body and is even uniquely capable of developing into a complete embryo by itself.[27]  During development cells can either replicate, multiply without modifying the organization of their DNA, or differentiate, multiply while changing their genetic potential.[28]  Once a cell has differentiated it can no longer form an entire organism by itself.[29]  Rather, the cell is limited to performing a particular function for the organism as a whole. 

Up until the eight-cell stage of development each cell of a mammalian embryo is totipotent.[30]  This ball of cells is called a blastoceol.[31]  At the next stage of development the cells multiply becoming 16 cells and the blasteoceol forms a blatocyst, a highly developed fertilized cell consisting of 100-300 undifferentiated cells to the point where it is ready to implant into the wall of the uterus.[32]  The cells that line this inner-wall have differentiated so they are now pluripotent.[33]  This means that if they are removed from this ball of cells, these cells could no longer form an entire embryo by themselves.[34]  However, pluripotent cells are able to form any of the different types of cells in the body – tissue, nervous, or muscular.[35]  It is these cells that are referred to as embryonic stem cells.[36]

Besides being pluripotent, able to differentiate into any type of cell in the human body, ESCs are also capable of unlimited undifferentiated proliferation in vitro.[37]  This means ESC can replicate indefinitely creating a multitude of exact copies of themselves.  This ability makes them exceptional tools for scientists to use because it provides scientists with a large supply of identical cells to experiment with.  These identical copies of ESCs are called stem cell lines. 

There are two other types of stem cells – adult stem cells and embryonic germ cells.  Discussions concerning the use of these other two types of cells for research are beyond the scope of this Note.   

B.  Stem Cells – The Potential

The ability of stem cells to differentiate into any cell type in the body has captured the attention of the medical community.[38]  Their potential uses range from replacement cells and tissues that can be used to repair damage caused by disease or injury to providing a means to study specific diseases or the developmental process itself.[39]  Stem cells can be differentiated in a controlled manner to form liver cells, bone cells, nerves cells, skin cells, blood cells, and more.[40]  These cells can then be implanted into an individual replacing the damaged cells or tissue.[41]  For victims of MD, spinal cord injury, severe burns, blood diseases and others, stem cell research provides a ray of hope that one day they could step beyond the confines of their disease or injury.

Stem cells further excite the medical community because of their potential to teach scientists and doctors alike about the cellular, genetic world they have been trying to conquer for the past two decades.[42]  The mystery of how an embryo develops has eluded scientists along with the intricacies of the majority of the genetic diseases.  ESCs provide a way for scientists to study the effects of the signals sent during the developmental process with the potential benefit of reducing birth defects and increasing the success of assisted reproduction.[43] 

Further understanding exactly what a diseased cell is doing, how it is performing or failing to perform, can help the medical community better treat and potentially cure these life-altering diseases.[44]  Studies of how a gene acts or fails to act have already resulted in the prevention and cure of several diseases.[45]  For example, understanding the genetic cause of PKU lead to the present treatment a diet free of phenylalanine.[46]  The discovery of a genetic disorder and the study of how that disorder behaves differently from other similar cells may provide the best hope for an environmental treatment of it.[47]  ESC’s provide an opportunity for scientists to thoroughly study cells carrying these genetic diseases, increasing the potential discovery of treatment and cures.[48]   

Outside of medicinal benefits and study, ESC can also help forensic scientists.  The new practice of identifying criminals genetically is often hindered by the size of the sample provided to the technicians.[49]  Using somatic cell nuclear transfer (SCNT), the DNA contained in the small sample can be inserted into an ESC and the sample size increased through the undifferentiated proliferation of the stem cell.[50]  Thus, providing the technician with a larger genetic sample for testing purposes. 

 Yet another benefit of stem cells comes to light under the guise of toxicity testing.[51]  Presently toxicity testing is conducted on animal cells or bacteria.[52]  If a drug is effective at low concentrations in vitro or in a petri dish, then there is the potential that it might be successful in vivo at low enough concentrations to not be toxic.[53]  Though these tests do shed some light on the toxic effects of chemicals, animal cells and bacteria cells are different from human cells and scientists cannot be sure without testing toxicity on human cells what potential effects there might be.[54] 

C.  Alternatives To Stem Cell Research

Opponents of ESC research argue that there are less controversial alternatives to research then ESC research such as research on ESC from umbilical cord blood and research on adult stem cells.[55]  Though both of these alternatives have had some success, neither provides a definitive solution and both have shown potential limitations to their use.[56]  At this early stage in stem cell research it is dangerous to limit our potential results by restricting our available resources.[57]  The delay in the development of stem cell technology equates to a loss of life for those desperately awaiting treatment. 

Further, two new studies released online by Nature on March 13, 2002 cast doubt on adult stem cell ability to convert into any cell type to fight disease or replace faulty organs.[58]  These two new studies cast doubt on previous research that had shown adult stem cells were capable of transforming into multiple types of cells found in the human body by showing that the real reason the cells dedifferentiated was the fact that they merged with the stem cells placed in the perti dish with them.[59]  These merged cells were found to contain twice the number of chromosomes as normal.[60]  The researchers that observed this phenomenon fear that this might have happened in the previous reports of successful transformation of cells fooling scientists into believing the adult stem cells had transformed themselves into less differentiated cells.[61]  These two research papers call into question all of the previous data generated with adult stem cells.[62]  In light of the uncertain expectations in all areas of stem cell research and in light of the enormous medical potential stem cell research possesses, all avenues of stem cell research should be utilized. 

D.  The Importance of Federal Funding

For the fiscal year of 2003, the United States government will spend $112 billion dollars on research and development with $26.5 billion directed to the National Institute of Health, which funds most of the United States Biotechnology research.[63]  The federal government funds around 85% of the sponsored research conducted.[64]  Therefore, the lack of funding from this arena has an inhibiting effect.[65]  The withdrawal of government funding will slow this research but it will not stop the research from continuing.[66]  Privately funded research and research sponsored overseas will continue to explore this realm of research and will do so without the comprehensive ethical oversight provided by United States human subject regulations.[67]  

II.  Stem Cells – The Regulations

Though relatively new in the public’s mind, embryonic stem cell research has been a matter of debate for some time.  The Ethics Advisory Board submitted a report to Congress as early as 1979 that declared it was acceptable for research on human embryos to be conducted as a means of evaluating In vitro Fertilization Clinics (IVF).[68]  The 900 - page report was never acted on and no legislation to this effect was ever created.[69]  When the government finally began regulating this field, the first Bush administration set forth an outright ban.[70]  At the start of the Clinton era, this moratorium was repealed followed by Congress passing the NIH revitalization Act of 1993, which created guidelines for fetal tissue transplantation.[71]  In 1994, an NIH report created by an interdisciplinary advisory panel appointed by the NIH strongly encouraged research to be conducted on unused embryos from IVF with the consent of parents and a narrow majority approved of the creation of the embryos for research purposes.[72]  Clinton publicly disagreed with these regulations and before they could be implemented the Department of Human Health and Services (DHHS) 1994 Appropriations Act blocked federal funding for ESC research by attaching prohibitions to the annual appropriations bill that funds the NIH.[73]  This amendment was called the Dickey Amendment and prohibited research resulting in the destruction of embryos.[74]   This amendment was reenacted annually until finally being allowed to expire on September 30, 2001.[75]

In 1998, the private culturing of ESCs fueled the smoldering debate concerning ESC research.  In 1999, The National bioethics advisory committee recommended funding for the derivation as well as the use of unneeded embryos.[76]  This report was considered by the NIH as they created their regulations.[77]  The NIH using a specific definition for embryonic stem cell determined that they could properly approve research conducted on derived stem cells without violating the DHHS Appropriations Act.[78]  Though Clinton approved of this interpretation of the DHHS appropriations act, President Bush the incoming president did not agree with the proposed NIH regulations.[79]  The Bush administration announced on August 9, 2001 to allow ESC research, but with more restrictions then those provided in the NIH proposed regulations.[80]  The present federal regulatory scheme does not affect privately funded research.[81]

The current state of regulation allows stem cell research to be conducted on pre-existing cell lines derived in an approved manner prior to President Bush’s August 9, 2001 announcement.[82]  To be eligible for federal funding the human embryonic stem cell line must have been derived from excess embryos created for fertility treatments by couples that gave their informed consent free of any financial inducements.[83]  NIH has released a list of 72 cell lines that meet this criteria.[84]  Research on any other cell lines will not be eligible for federal funding.  Further, there are restrictions on the type of research that can be conducted in these cell lines.[85]

III.  Stems Cells – The Balancing Factors

In determining appropriate regulation several factors should be considered including morality, potential loss of leadership position, lack of utility in existing stem cell lines, lack of diversity in cell lines, and loss of scientist.  All of these factors deserve consideration when the government determines whether or not it is able to support embryonic stem cell research and no one factor should be allowed to dominate this balancing approach.  Presently, the moral position is given far too much weight in this analysis.  In setting forth and analyzing the factors below this Note will argue that in light of the competing moral positions this factor should be given the same weight as all other factors in this balancing approach.  

A.  Morality

As presented previously the potential benefits of ESC research are immense and the research has only just begun.  Now that a stem cell has been described and its potential benefits recited, the question becomes why is the federal government hesitant to support this research?  There are many sides to the debate over ESC research.  And many of these sides are not new arguments specific to the ESC debate such as, the clash of religion and science, the promise of technology to improve man’s condition, the danger that this progress will lead to the destruction of humanity along with others.[86]  ESC research merely provides the conduit for society science and religion to once again address these issues.[87] 

The moral debate concerning ESC research is an ever-expanding topic.  Further, there are competing goods at stake concerning ESC regulations.[88]  Morality is an elusive topic in a nation as large as the United States making it hard to claim that a single morality exists.  This Note does not claim to cover every facet of the argument but it will address the central morality arguments for both sides.  The basic moral arguments against ESC research concern the origination of ESCs and how the developments in ESC technology will affect society.  The basic moral arguments for ESC research is the fact the excess embryos are designated for destruction whether or not they are used for research, and the fact that by refusing to conduct this research, millions of individuals will suffer from diseases that could potentially be alleviated by ESC research developments.

i.              Origination of ESC

Hidden behind the ESC’s glowing potential lurks the shadow of its origination.  Opponents of ESC research fear we are treading upon the value of human life and opening a pandora’s box to the moral and ethical dilemmas inherent in sacrificing another’s potential life for the good of society.[89]  This fear is based on the fact that when the ESCs are removed from the pre-embryo or blastocyst stage, the pre-embryo is destroyed, meaning it can no longer develop into an embryo and later into a fetus.[90]  This destruction of a potential life leads the conservative pro-life sector to denounce ESC research as immoral.[91] 

Supporters of ESC research argue that the embryos used to create ESCs are designated for destruction as it is and as such, it is more acceptable to use the embryos to promote life then to simply discard them as waste.[92]  To better understand their argument one needs to understand a little about the in vitro fertilization procedure.  The excess embryos used to create ESC lines come from the in vitro fertilization process.[93]  This process, IVF, is an uncertain procedure even though it has been practiced in private clinics for many years.  Because of the high cost of the procedure and its uncertain success, patients often remove and fertilize multiple eggs.[94]   These excess embryos are then stored to be implanted later if the first attempt at implantation is unsuccessful.[95]  Generally, if the first process is successful the couple can then chose to either discard these embryos, use them later to create another child, donate them to other couples, or donate these to research.  If the first attempt is unsuccessful, these stored eggs can be used in a second implantation procedure.[96]   

Opposition towards the use of these excess embryos to create ESCs appears very hypocritical in light of the fact that there is a lack of a moral uprising over the IVF procedures themselves, which create the excess embryos and this situation.  The cryogenic freezing process used to store embryos for later use destroys 25% of the embryos stored.[97]  One source speculates that hundreds of thousands of unused embryos have been destroyed in fertility clinics.[98]   Yet, this enormous waste of life has not raised nearly the issues that the use of few dozen embryos to create ESC for medical research has in the public moral spectrum.[99]

Presently, no law exists preventing the destruction of these embryos, nor is such a law likely to be implemented in light of the constitutional right to not procreate and the established abortion laws.[100]  The general practice of the government is to stay out of the procreative choices of individuals, therefore making it difficult for the government to make the leap to requiring the excess embryos to be either implanted or adopted.[101]  In this situation, the embryos ultimate designation is destruction, and the only question remaining is how the embryo will be destroyed.   

President Bush himself rationalized allowing federal funds to support ESC research on existing stem cell lines because the life and death decision has already been made.[102]  Using his own rationalization, President Bush should also support the derivation of new stem cell lines from the unwanted excess embryos created through the in vitro fertilization process.  Each year, thousands of spare embryos created in infertility procedures are routinely destroyed at the request of their progenators.[103]  This makes the relevant ethical question whether these embryos should simply be thrown away or used for human benefit.[104]  To those desperately needing the potential cures promised by ESC research, the useless, wasteful destruction of these potential sources of life symbolize the destruction of their hopes and dreams.[105] 

According to data from the Center for disease Control National Center for Health Statistics, 3,000 Americans die every day from diseases that may in the future be treatable with ESC therapy[106], implying that it is not ethical to not support research that could alleviate the suffering of millions of Americans afflicted with devastating diseases.[107]  Sweden, the country presently leading in ESC research, is an example of a country that believes the enormous medical benefits derived from ESC research establishes that this research is in the best interests of their public health and therefore, ethical.[108]  Advocates of ESC research in the United States believe our government should make the same determination.

There are strong moral arguments both for and against ESC research and it is important that these arguments be considered when ESC regulations are determined.[109]   However, morality is only one factor of several that should be considered in determining appropriate ESC regulations and in light of the fact that morality speaks so strongly on both sides of the argument, legislators should not give this factor greater weight then the other factors used in this balancing approach.

B. Leadership

Another concern is how ESC technology will be used by nations with less respect for human life then the United States.[110]  The example commonly used is China.  It isn’t hard to speculate that the Chinese government, not known for respecting human life to the degree of the United States, will use the technological advances of the United States to progress beyond their cloning of rabbit embryos containing human DNA to clone human fetuses for experimentation or to use the ability to screen for genetic disorders to produce children made to specification.[111]  However, the United States is not considered the leading nation when it comes to ESC research and as such whether or not we participate in this research is not going to affect China or any other countries ability to abuse the technology.  In fact, if we do back away from this technology, it will more then likely weaken our position to influence its use, which in the end may be the greater moral wrong.

Examining the present situation of countries that refused to enter the race to discover the human genome or refuse the participate in stem cell research, provides the background to predict what will happen to the United States if we continue to strictly regulate stem cell research. 

Examining, other countries where the government has either failed to support a rapidly growing industry or crippled the industry with strict regulations shows such government intervention has lead to the countries being left behind in the specific technology.[112]  Italy is a prime example of country that has lost hope for actively participating in genomic research.[113]  The strict regulation by the conservatively controlled government has lead to the flight of their young scientists to other countries, shrinking intellectual property patent awards, and the ultimate outcome of the country being far behind in genomic technology.[114]  German researchers are also having problems with delays in their government resulting in ESC research being crippled by delays awaiting for government approval.[115]  Whereas Sweden with very lax stem cell regulations has become the largest single source of stem cell lines approved on the NIH stem cell line registry.[116]  Canada observing that their lack of funding for human genomic research had resulted in a loss of scientists to the United States has made great efforts to reenter the genomic revolution especially in the area of stem cell research.[117]  Using large tax incentives, providing investment opportunities and a biotechnology commercialization fund has resulted in drawing its scientists back into Canada and moving itself into a position of leadership in stem cell technology.[118]

C.  Material Limitations

Placing a limit on the number of cell lines available may place roadblocks to medical progress, some of which may take years to overcome.[119]  Pre-emptively limiting the materials with which researchers are able to work early in its progress may be extremely detrimental costing years and possibly even lives.[120]  Some critiques claim the only parties to benefit either directly or indirectly from Bush’s stem cell policy are the handful of companies whose derived stem cell lines are approved by the NIH.[121]  Under the Bush policy, no new cell lines can be created and be eligible for federal funding.[122]  This creates several difficulties with our ability to benefit from the limited ESC research that has been and is being conducted presently.  

i.              Utility

The NIH initially claimed that all the cell lines identified and listed in the registry were viable, meaning they shared the expected characteristics of human ESCs.[123]  However, the NIH has admitted that there might be supply problems adding that the derivations of the cell lines are still in the early stages of characterization and thus may not be immediately available.[124]  In fact when further questioned Tommy Thompson, the President’s Secretary for Health and Human Services, conceded there were only 24 stem cell lines currently useable.[125]  Further concerns include whether or not the stem cell lines are actually immortal and whether they may in the future accumulate genetic errors.[126]  Additionally there is the problem with the FDA restrictions on Xenotransplant products that would foreclose use of any of the presently derived cell lines in a cellular therapy context.[127]  All of the stem cells presently in existence are believed to qualify as Xenotransplantation products under these FDA guidelines because the cells were grown using mouse feeder cells and bovine serum.[128]  A new technique has been developed to sustain human ESC without the use of animal products, but any cell lines developed and maintained by this technique would not be available for federal funding under the present regulations.[129]  Therefore, their utility as potential future therapies is questionable.

ii.         Diversity

Limiting research to be conducted only on the 72 existing stem cell lines clearly limits the genetic diversity available for stem cell research.  While human beings have much in common, are genes are diverse.  It is estimated that about 7% of the proteins differ from individual to individual.[130] 

A common problem with any tissue or cellular transplantation is the potential for immune rejection.[131]  Immune rejection problems happen because the human body has evolved a mechanism to protect itself from foreign invaders.[132]  One method of protecting itself uses cell surface proteins known as human-leukocyte-associated antigens.[133]  These antigens are basically cellular fingerprints and just as it is rare for two individuals to share the same fingerprints it is rare for two individuals to share the same antigen markers on their cellular surface.[134]  When the cells of the immune system identify a cell with foreign HLA antigens, the cell is destroyed, this complicating the transplantation process.[135]  In order for a transplant to be successful the HLA antigens on a cells surface must be matched as closely as possible.  The ability to match these antigens is severely restricted when the starting pool for HLA diversity only consists of 72 possible options.

The diversity of the 72 stem cell lines is further challenged by the known sources for these stem cell lines.  The majority of these cell lines were derived from Caucasian couples.[136]  This lack of racial diversity in the stem cell lines is unlikely to be compensated for by the private sector.[137]  The private sector’s sole purpose for conducting the research is to make a profit.[138]  A profitable business rarely directs its attention to the needs and desires of the minority rather their focus is on the majority population as well.[139]  Meaning the minority’s genetic interests will be under addressed in the ESC research arena.

iii.    Brain Drain Phenomenon

Scientists work where there is funding and support for the type of research they desire to perform.  The federal government funds around 85% of sponsored research conducted in the United States.  Therefore, it is important to have federal funding for the field of research a scientist wants to research.  Even though funding is now available the restrictions on availability of stem cells to perform the work, the restrictions on the type of research that can be conducted on the stem cell lines once you get access to them, the requirement that there is no intermingling between federally funded research and privately funded research, the licensing restrictions on several of the available stem cell lines and the restrictive hostile environment towards ESC research all combine to discourage scientists to base their research efforts in the United States when Britain, Sweden, and Canada to name a few are far more supportive of their research efforts.[140]  In fact, Britain is considered one of the most attractive research and development locations in Europe.[141] 

Private companies holding stem cell lines such as CyThera, Bresagen, and ES Cell International will provide their cell lines for free but will ask for first rights to license any resulting intellectual property.[142]  Recognizing these disincentives, NIH has drawn up an agreement with WiCell,[143] that provide human ESC with as few strings as possible.[144]  Further researchers can avoid obligations by seeking to work with private companies.[145]

Ironically the list of approved cell lines released by the NIH represents a casualty list reflecting how past and present regulations have already impacted ESC research in the US.[146]  Only 20 of the 72 stem cell lines originate from US laboratories and only 7 of those from public laboratories.[147]  The countries conspicuously absent are those still burdened by a moratorium on ESC research such as France, Germany, and Italy.[148]  The effects are obvious, if a government prevents its countries scientists to research in a particular field it will lose its researchers, lose the economic benefit resulting from such research, and have a hard time reentering the research field after being lax at the technologies inception.[149]  

IV.          Recommended Regulations

There should be regulations that govern federally funded stem cell research, but these regulations should be more closely mirror with the public’s actual concerns.  I propose that federal funding should support the derivation of embryonic stem cell lines from the excess IVF embryos.  These stem cell lines should be derived from excess in vitro fertilization eggs donated by couples that gave their informed consent free of any financial inducements.  This will allow us to increase the sample cell lines in existence creating greater diversity among the stem cell lines.  Further, this will allow scientists to create stem cell lines that would not violate the FDA Xenotransplantation regulations, by creating cell lines without the use of any animal materials.  It is in the best interests of the United States to put itself at the forefront of this research so they can understand the technology and help influence its application in the medical community.

V.               Conclusion

     In light of the detrimental effects the present ESC regulations have on the United States scientific and medical communities, the present regulations on ESC research need to be reexamined.  There is no reason to severely restrict federally funded research by limiting it to 72 cell lines that are not representative of the population as a whole.[150]  There is no reason to not support using the excess embryos from in vitro fertilization clinics to establish further cell lines.  In balancing the factors that should be considered the morality concerns about ESC research are outweighed by the potential benefits that could result, by the extensive knowledge waiting to be discovered, and by the loss of the United States position as a leader in the scientific medical community. 

The regulations recommended in this Note will still support the public policy of not promoting the destruction of the embryo because only embryos already designated for destruction may be used and the suggested regulations will not support the creation of embryos for research purposes alone.  Further, these suggested regulations allow for ESC lines that would not violate FDA regulations to be created thereby not impeding future transplantation therapy.



[1] Robert Lee Hotz, Book Review Our Posthuman Future, Los Angeles Times, May 5, 2002

[2] Id.

[3] President George W. Bush, Remarks by the President on Stem Cell Research, August 9, 2001 (transcript available at http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html).

[4] Similar arguments are made to support therapeutic cloning for use with stem cell technology as are made with ESC research.  Jeremy Manier, Cloning Backers bank on science, Chicago Tribune Company Chicago Tribne, May 7, 2002.  The Brownback proposal would ban all human cloning while the Kennedy and Feinstein bill would permit cloning for research.  Id.  Therapeutic cloning is claimed to be a misdescriptive term for cells used in research regarding concerous cells cloned because the clone is of the tumor not the individual and as such these cells contain numerous genetic flaws.  Id.  

[5] On August 25, 2000 NIH released guidelines to regulate federally funded embryonic stem cell (ESC) research.  After consulting the Department of Health and Human Services (DHHS) General Counsel, NIH determined that federally funded research on human ESCs would not violate the DHHS appropriations Act of 1999.  The DHHS Appropriations Act prohibited human embryo research, and the director of NIH determined ESCs are not by definition human embryos.  Neil Monro, Political Science, The National Journal, September 16, 2000.  This bold step by NIH towards promoting ESC research ignited the ESC research debate raising it to a status of such importance that it became a presidential election issue.  President Bush campaigned against supporting embryonic stem cell research and many proponents of such research feared the action he would take once in office.  Surprisingly Bush did not choose to ban ESC research.  Rather, Bush chose to allow federally funded research to continue but within specified limitations or restrictions. 

[6] NIH Human Embryonic Stem Cell Registry, http://escr.nih.gov/.

[7] Id.

[8] Id.

[9] Dawkins, Richard, The Selfish Gene 21-22, (1989).

[10] Id.

[11] Id. at 22.

[12] Stuart Ira Fox, General Physiology, fifth edition, 1996, 9.

[13] Albrets, Bruce et al., Molecular Biology of the Cell 36 (3d ed. 1994).

[14] See Fox, 9.

[15] The cells that compose the four tissues differ greatly.  Neurons and neuroglia are the cells of the nervous tissue.  The neuron basically consists of three parts: a cell body, dendrites and axons, whereas the neuroglia bind the neurons together.  Epithelial tissue cells consist of membrane cells and gland cells.  Connective tissue cells consist of blood cells, cartilage, bone and connective tissue proper.  All of these cells differ from one another in function and form.  Muscle tissue consists of either the skeletal muscle cells, the long thin fibers or myofibers, cardiac muscle cells, the short branched interconnected myocardial cells, and smooth muscle cells arranged longitudinally or circularly throughout the different areas of the body.  Id.   

[16] Most cell in the body have a single nucleus.  The nucleus is surrounded by a nuclear envelope which is composed of an inner and outer membrane which at various points are fused together by nuclear pore complexes.  Each of these complexes has a central opening or nuclear pore through which small molecules may pass by diffusion allowing the nucleus to communicate with the cell that houses it.  RNA the messenger protein passes through these pores.

[17] Nesse, Randolph M., PH.D et al., Why We Get Sick The New Science of Darwinian Medicine, 92, 1995.  When this is multiplied by the ten trillion cells in the human body our DNA would stretch 20 billion kilometers about the distance to the planet Pluto. 

[18] About 95% of the DNA is never translated into proteins.  The remaining 5% of human DNA can be divided into 100,000 protein-coding genes.  Id.

[19] www.nih.gov/news/stemcell/achieve.htm “What would you hope to achieve from human pluripotent stem cell research?, National Cancer Institute, April 26, 2000.  Last visited May 15, 2002

[20] www.acs.ucalgary.ca/~browder/Cell_Diff.html, last visited May 15, 2002.

[21] Id.

[22] The nucleus is surrounded by a nuclear envelope, which is composed of an inner and outer membrane, which at various points are fused together by nuclear pore complexes.  Fox, at 57.  Each of these complexes has a central opening or nuclear pore through which small molecules may pass by diffusion allowing the nucleus to communicate with the cell that houses it.  Id.  RNA the messenger protein passes through these pores.  Id.

[23]  Id.  Each gene is several thousand nucleotide pairs long.  The DNA in a human cell contains 3 billion to 4 billion base pairs.  This is enough genetic information to code for at least 3 million proteins, but only a fraction of our DNA is actually used to code for proteins.

[24] Each gene contains the code for the production of a particular type of messenger RNA (mRNA).  Id. at 57.  This messenger RNA provides the code for a specific type of protein.  Id.  Genetic expression occurs in two stages genetic transcription, the creation of the RNA in the nucleus, and genetic translation, the creation of the protein from the mRNA after it has left the nucleus through one of the nuclear pores.  Id. At 58

[25] See Nesse at 96.

[26] Alberts, Bruce, et al., Molecular Biology of the Cell 32 (3d edition 1994).

[27] Department of Health and Human Services, Stem Cells:  Scientific Progress and Future Research directions F-10 (2001), (available at http://www.nih.gov/news/stemcell/fullrptstem.pdf).

[28] Cite needed.

[29] Id.  There is the rare potential for a cell to dedifferentiate, but this phenomenon is rareand outside the scope of this paper.

[30] Alberts, Bruce et al., Molecular Biology of the Cell 1058 (3d ed. 1994).

[31] http://www.ivf.com/blasteocyst.html

[32] Id.

[33] Id.

[34] Department of Human Health and Services, Stem Cells: Scientific Progress and Future Research Directions, 5 (2001), (available at http://www.nih.gov/news/stemcell/fullrptstem.pdf).

[35] Id..  T. Wakayama et al., Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer, Science 740, April 27 2001.  N. Lumelsky et al., Differentiation of embryonic stem cells to insulin-secreting structures similar to Pancreatic Islets, 10:1126 ScienceExpress, April 26, 2001.

[36] Id.  This note only addresses the legal issues surrounding embryonic stem cells.  Another source of stem cells are the embryonic germ cells that come from the primordial germ cells of the developing fetus or embryo.  Department of Health and Human Services supra note ____.  The tow types of ESCs are similar in man respects, but differ in their origins and growth characteristics.  Id..

[37] James A. Thompson et al., Embryonic Stem Cell Lines Derived from Human Blastocysts, 282 Science 1145 (1998).

[38] See National Institute of Arthritis and Musculoskeletal and Skin Disease (NIAMS), NIH, March 25, 1999.  Response to Senator Specter’s Inquiry “What would you hope to achieve from stem cell research?” In the future stem cells may be introduced into areas with damaged bone or cartilage aiding in problems such as ostearthritis or refilling the large gaps in bones following fractures.

[39] Steven L. Teitelbaum, Allow Research Cloning; There are Clear and Appropriate Ways to Permit Important Research Using Cloning Techniques, While Banning the Cloning of Human Beings, St-Louis Post-Dispatch, April 18, 2002.

[40] Gearhart, J.D., New Potential for Embryonic Stem, 282 Science 1061-1062, 1998. 

[41] Irving L. Weisman and David Baltimore, Disappearing Stem Cells Disappearing Science, Science 601, April 27, 2001.  Like any tissue or organ transplantation, ESC transplantation would requires addressing the problem of immune rejection.  One solution to immune rejection is to use somatic cell nuclear transfer because using a patients own DNA may provide one way to circumvent the bodies own natural defense mechanism to attack any foreign body it comes across.  Bruce Alberts, Please Don’t Call It Cloning, 295 Science 1237, February 15, 2002.

[42] Department of Human Health and Services (DHHS), Stem Cells: Scientific Progress and Future Research Direction, 17 (2001), (available at http://www.nih.gov/news/stemcell/fullrptstem.pdf); Ethical Issues in Human Stem Cell Research, 1 Report and Recommendations of the National Bioethics Advisory Commission (NBAC) 23, September 1999.

[43] Department of Human Health and Services, Stem Cells: Scientific Progress and Future Research Direction, ES-1 (2001), (available at http://www.nih.gov/news/stemcell/fullrptstem.pdf);

[44]Id., Ronald M. Green, Stopping Embryo Research, 9 Health Matrix 235, 237, Summer 1999.

[45] See Neese at 106.

[46] Id.

[47] Id.

[48] Bruce Alberts et al., Please Don’t Call It Cloning, 295 Science 1237, February 15, 2002.  This benefit of ESC research is limited to using somatic cell nuclear transfer (SCNT) to import in a patients DNA containing the disease that scientists want to study.  Recent legislation passed by the House of Representatives and under consideration by congress to ban the cloning of human beings actually describes the use of SCNT.  If this proposal is passes this benefit of ESC research would be severely impaired, even though SCNT performed on an ESC would not result in the clone of a human being because ESC are incapable of developing into an entire human being.  The outcome of SCNT on an ESC is not to create a copy of the potential tissue recipient, but rather to make tissue that is genetically compatible with that of the recipient. 

[49] NBAC, supra note 42.

[50] Id.

[51] Department of Human Health and Services, Stem Cells: Scientific Progress and Future Research Direction, 17-18 (2001), (available at http://www.nih.gov/news/stemcell/fullrptstem.pdf).

[52] Stuart Ira Fox, Human Physiology, Fifth edition 1996, 5

[53] Id.

[54] The toxicity test process usually starts with testing drugs at very low concentrations on in vitro animal or bacterial cells.  Id.  If there is success with the low drug concentration, then the testing is moved to animal testing and then on the clinical trials.  Id.  More then 90% of the drugs tested in trials on animals are considered too toxic to proceed.  Id.  If it could be observed earlier on human cells that a drug was likely to be toxic this could decrease the testing on animals because less drugs would pass through the first stage in the process.

[55] Gary L. Bauer, Stem Cell Research; Advocate and opponent debate the merits of studies in which scientists destroy human embryos in hopes of curing diseases CON, The Dallas Morning News, September 3, 2000.  A number of studies have shown that ESCs could arise from another source such as adult stem cells derived from adult bone marrow cells.  Id.

[56] Adult stem cells are difficult to replicate and in limited supplies in the human body with the numbers decreasing as patients age.  Greg Winter, New Alchemy: Bone and Cartilage from a snippet of skin; The New York Times Company, June 20, 2000.

[57] Id.

[58] Cloning Studies cast Doubt on Efficacy of adult stem sells, Genomics and Genetics Weekly, April 12, 2002.; Cloning Studies cast doubt on efficacy of adult stem cells, Stem Cell Week, April 8, 2002.

[59] Id.

[60] Id.

[61] Id.

[62] Id.

[63] David Crane, Let’s Learn How to Fight the Sandwich Effect, Toronto Star, April 24, 2002.

[64] Association of University Technology Managers, Inc., Autm Licensing Survey, FY 1999, survey Summary 1 (2000), available at http://www.autm.net/surveys/99/survey99A.pdf.

[65] Id.

[66] Robert P. Lanza et al., The ethical reasons for Stem Cell Research, 292 Science 1299, May 18, 2001.  

[67] Id. 

[68] Science August 24, 2001, 1401

[69] Id.

[70] Alexander Morgan Capron, Stem Cells: Ethics, Law and Politics, 20 Biotechnology L. Rep. 678, 697 (2001).

[71] Federal Funding of Tissue Transplantation Research, 58 Fed Reg. 7457, Jan. 22, 1993.

[72] Id.

[73] The Balanced Budget Downpayment Act, I, Pub. L. No. 104-99 128, 110, Stat. 26 (1996)

[74] See Consolidated Appropriations ---- FY 2001, Pub. L. No. 106-554, 510, 114 Stat. 2763; Micheal Casey, Can we rebuild the US Health Care System Medical Industry Today, January 18, 2001. 

[75] Id.

[76] Arthur, Breaking the Stalemate: A Prospective Regulatory Framework for Unforeseen Research Uses of Human Tissue Samples and Health Information, 34 Wake Forest L. Rev. 737, 746.

[77] August Gribbon, NIH Releases Rules for Research on Embryonic Stem Cells, The Washington Times, August 24, 2000. 

[78] Ellen J. Flannery and Gail H. Javitt, Analysis of Federal Laws Pertaining to Funding of Huamn Pluripotent Stem Cells, 2 Ethical Issues in Human Embryonic Stem Cell Research D-6 – D-9, January 2000. 

[79] Id.

[80] Constance Holden, NIH’s List of 64 Leaves Questions, 293:5535 Science 1567, August 31, 2001

[81] Id.

[82] Jeffery L. Fox, US Deliberates on Embryonic Stem Cells, Cloning, 19:9 Natures Biotechnology 791, September 2001.

[83] Id.

[84] Id.

[85] Jeffery L. Fox, US Deliberates on Embryonic Stem Cells, Cloning

[86] Eric Cohen, New Genetics, Old Quandaries, The Weekly Standard, April 22, 2002

[87] Remarks on Human Cloning Technology, Public Papers of the President, April 15, 2002.  The president continued “we can pursue medical research with a clear sense of moral purpose or we can travel without an ethical compass into a world we could live to regret.”  Life is a creation not a commodity --- speaks more to emotion than to facts.

[88] See Tina Hesman, Ban’s Critics, Backers Fear Consequences, St-Louis Post Dispatch, April 14, 2002.

[89] Ronald M. Green, supra note 44.

[90] See James A, Thompson et al., Embryonic Stem Cell Lines Derived From Human Blastocysts, 282 Science 1145 (1998)

[91] Alexander Morgan Capron, Stem Cells: Ethics, Law and Politics, 20 Biotechnology L. Rep. 678, 687 (2001); Green supra note 44.  This argument is flawed because what is being evaluated or weighed is how an embryo destined for destruction should be destroyed. 

[92] “If they are going to be destroyed anyway, shouldn’t they be used … for research that has the potential to save and improve other lives?”  President George W. Bush, Remarks by the President on Stem Cell Research, august 9, 2001 (transcript available at http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html).

[93] The in vitro fertilization process involves artificial insemination of an egg in a laboratory.  Infertility and IVF Center, St. Louis, Mo., In Vitro Fertilization (available at http://www.ivfctrstl.org/ht-ivf.htm.  The resulting embryo is either implanted in the uterus or undergoes cryogenic preservation after it develops to the four or eight cell stage.  Id.  Cryogenic preservation allows embryos to be preserved and stored for extended periods of time in liquid nitrogen.  Jennifer Marigliano Dehmel, To Have or Not To Have:  Whose Procreative Rights Prevail in Disputes Over Dispositions of Frzen Embryos?, 27 Conn. L. Rev. 1377 (1995).  If another attempt at pregnancy is desired than the embryos may be thawed and the implantation process attempted again sparing the female from the physical stress and pain of hormone stimulation and egg retrieval as well as sparing the couple the excess cost of repeating the entire procedure a second time.  Lee M/ Silver, Remaking Eden, 95 (1998).

[94] http://www.ivf.com.html

[95] http://www.ivf.com/blasteocyst.html; A process called Cryogenic preservation allows embryos to be stored for many years allowing IVF users to return years later and attempt another pregnancy. http://religious tolerance.org/res_stem1.htm.   Last visited May 15, 2002.

[96] See supra note 64.

[97] http://www.religiostolerance.org/res_stem2.htm Last visited May 15, 2002.

[98] Carl T. Hall, “The Forgotten Embryo: Fertility clinics must store or destroy the surplus that is part of the process,” SF Gate News, at: http://www.sfgate.com/ Last visited May 15, 2002.

[99] Carl T. Hall, “The Forgotten Embryo: Fertility clinics must store or destroy the surplus that is part of the process,” SF Gate News, at: http://www.sfgate.com/ Last visited May 15, 2002.

[100] The right not to procreate has been upheld in the courts.  Davis v. Davis held that ordinarily the party wishing to avoid procreation should prevail assuming that the other party has a reasonable possibility to achieve parenthood by means other then the use of the pre-embryos in question.  Davis v. Davis, 842 S.W.2d 588, 593 (Tn. 1992).  Further the court itterrated that if the desire was to donate the embryos to another couple the objecting party has the greater interest and should prevail.  Id.  The court in Litowitz v. Litowitz held that the wife’s interest in having the embryo’s implanted in a surrogate mother was not sufficient to outweigh the father’s interest to not procreate.  Litowitz v. Litowitz, 102 Wash. App. 934. 

[101] Both Davis v. Davis and the Lithowitz case support the right to not procreate.  In light of this existing precedent, it would be difficult for the courts to force the progenitors to implant the excess embryos either in themselves or in adoptive parents.  Further, the present abortion laws approve of the destruction of the embryo for any reason at the will of the mother up to the third trimester which makes it difficult to argue that the embryo which can be destroyed for any reason up to that point has a right to life when it exists outside the mother.

[102] Jeffery L. Fox, US Deliberates on Embryonic Stem Cells, Cloning, 19:9 Nature Biotechnology 791  September 2001.  Further one of the co-authors of the successful restrictive German ESC regulations passed in February of this year stated in support of the regulations restriction to cell lines created before the passage of the regulations “we cannot cancel the fact that the embryos were already killed for the existing cell lines.”  Again this logic should extend to cover embryos designated for destruction after their use in the IVF procedure is no desired.  Gretchen Vogel, German Researchers Get Green Light, Just, 295 Science 943, February 8, 2002.

[103] Lanza, supra note 66.  This same dilemma is being examined in Australia where ACT Chief Minister Jon Stanhope points out that the 70,000 spare embryos in frozen storage in Australia if not used for stem cell research will eventually simply be thrown away.  Stanhope continues to support that to cut off research in this field is to cut off hope ofr a better healthier society.  Monika Boogs, Stem-Cell research Breakthroughs Will Light Up Our Lives, Says Cross, Global News Wire, April 12, 2002.

[104] Id.

[105] Delays in ESC research have a real cost in terms of human suffering.  Data from the Center for Disease Control’s Nationa; Center for Health statistics states that approximately 3,000 Americans die everyday from diseases that may in the future be treatable by ESC derived cells and tissues.  Robert P. Lanza et al., The ethical reasons for Stem Cell Research, 292 Science 1299, May 18, 2001.

[106] Lanza supra note ____.

[107] Steven L. Teitelbaum, Allow Research Cloning; There are clear ways to permit important research using cloning techniques, while banning the cloning of human beings, St. Louis Post Dispatch, April 18, 2002.

[108] David Crane, Let’s Learn How to Fight the Sandwich Effect, Toronto Star, April 24, 2002.

 

[110] Id.

[111] Id.

[112] Id.

[113] See Nature Biotechnology, 516, June 2001

[114] Nature Biotechnology, 516, June 2001

[115] Gretchen Vogel, German Researcher Get Green Light, Just, 295 Science 943 February 8, 2002.

[116] Science, Cloning Carbon copy clone is the real thing, 1443, February 22, 2002.  Sweden profited from taking an early stand on ESC research.  The government determined that it was in the best interest of the country’s public health to pursue ESC research and thus the research was determined to be ethical.  Steps Sweden has taken to develop its bioscience research are continued and increased investments in education and in research, investments in multidisciplinary research, flexible public financing for collaborative projects between a company and a university group, increased early stage funding, clear rules and regulations, and increased public awareness and knowledge.  Its position at the forefront of this research is surprising considering the size of the countrey and the resources available.  David Crane, Let’s Learn how to fight the Sandwich Effect, Toronto Star, April 24, 2002.

[117] Nature Biotechnology, 523, June 2001

[118] Id.

[119] Id.

[120] Id.

[121] Liz Fletcher, US Stem Cell Policy Comes Under Fire, 19:10 Nature Biotechnology 893, October 2001.

[122] Id.

[123] Id.

[124] Id.

[125] Id.

[126] Id.

[127] Id.  Presntly the FDA  will not allow any procedure involving the transplantation, implantation, or infusion into a human recipient of either live cells, tissues, or organs from a non-human animal source, or human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs.  Food and Drug Administration, Guidance for industry:  Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans (2001) (available at http://www.fda.gov/cber/gdlns/clinxeno0201.pdf).  There is a general concern over the spread of infectious agents of animal origin into the human population that provides the basis for these restrictions.  Id. 

[128] Jill Carroll and Jim Vandehei, Mouse Cells in Stem Lines May Limit Use, Wall ST. J., Aug. 24, 2001 at A3.

[129] Chunhui Xu et al., Feeder-Free Growth of Undifferentiated Human ESC, 19 Nature biotechnology 971 (2001).

[130] See Nesse, supra note 17 at p. 94.

[131] Bruce Alberts et al., Molecular Biology of the Cell 1229-30 (3d ed. 1994).

[132] Id.

[133] Id.

[134] Id.

[135] Id.

[136] Jon Entine & Sally Satel, Inserting Race into the Stem Cell Debate, Wash. Post, Sept. 9, 2001, at B1.

[137] Id.

[138] Ceci Connolly, Justin Gillis & Rick Weiss, Viability of Stem Cell Plan Doubted, Wash. Post, August 20, 2001.

[139] Id.

[140]

[141] Edward Baumgartner, Novartis says Animal Rights Activists Make It Wary of Increasing Investment in UK,

[142] Liz Fletcher, US Stem Cell Policy Comes Under Fire, 19:10 Nature Biotechnology 893, October 2001.

[143] This is an institute associated with the nonrofit organization Wisconsin Alumni Research Foundation (WARF, Madison Wisconsin).  Id.

[144] Id.

[145] Id.

[146] Liz Fletcher, US Stem Cell Policy Comes Under Fire, 19:10 Nature Biotechnology 893, October 2001.

[147] Id.

[148] Id.

[149] Id.

[150] Jon Entine & Sally Satel, Inserting Race into the Stem Cell Debate, Wash. Post, Sept. 9, 2001, at B1.