Biotech: What to Expect

Over the past fifteen years, the pro-life movement has succeeded in enacting some modest limitations on embryo-destructive research. Passage of these depended heavily on Republican control of the Congress, and their defense in the past eight years depended heavily on a Republican president willing to use his veto pen. The new political environment puts all of these achievements at grave risk and makes further steps essentially impossible for the time being.

The crucial story of the past several years in stem-cell science has been the story of newly emerging sources of pluripotent stem cells. What began as a series of speculative proposals early this decade and then coalesced into a few avenues of research between 2004 and 2006 has become the story of somatic-cell reprogramming.

In November 2007, two teams of researchers (one in Wisconsin and one in Japan) announced they had successfully transformed regular human adult skin cells into what appeared to be the equivalent of embryonic stem cells without using human embryos. Since then, several crucial advances have made the technique more efficient, more effective, and safer, and the cells produced by this technique (called “induced pluripotent stem cells,” or “iPS cells”) have so far continued to display all the characteristics attributed to human embryonic stem cells. These techniques not only avoid any ethical concerns (concerns, of course, that researchers in the field generally do not share), but they offer a far cheaper and easier method of producing genetically matched or selected pluripotent stem cells, which makes them appealing to researchers.

As a result, this technique has begun to overtake the use of embryos in many stem-cell labs. At last count (in the fall of 2008), there were approximately eight hundred laboratories using iPS cells in their work, which has cut sharply into the number of those using human embryos or cells derived from embryos. If the cells involved continue to prove equal to human embryonic stem cells in abilities and characteristics, this technique offers a genuine alternative to the destruction of embryos for nearly every purpose to which human embryonic stem cells and human cloning for research have been proposed or employed. The chief exception is the study of human development itself, which certainly has some devoted champions in the scientific community but which makes for a significantly less appealing political message than does the pursuit of regenerative medicine.

To date, no therapeutic applications of embryo-derived cells have been demonstrated, and only one preliminary human trial has been approved by the FDA (though it has yet to begin). The work, however, is proceeding, and the political debate about the research has certainly raised its profile and thereby brought private and some state funding pouring in. There have been no game-changing breakthroughs in the use of embryonic stem cells in recent years, but researchers remain confident of their potential utility, and their use will certainly continue even as work with iPS cells will likely overtake embryonic stem-cell research in volume and scope.

Research in human cloning is also proceeding. Given the number and quality of labs around the world currently pursuing human cloning techniques and the increasing efficiency and success of cloning techniques in nonhuman primates, it is reasonable to expect the successful creation of a human embryo by cloning in the next year or two.

The most significant obstacle to such success at this point is probably the limited supply of human eggs for research, which severely restricts the ability of researchers in the United States and in most of Western Europe to engage in large-scale cloning experiments of the sort that led to the first cloning of primates a few years ago. For this reason, significant research efforts have begun to explore means to produce eggs”for instance, by transforming iPS cells or embryonic stem cells into human egg cells, by using or improving damaged or low-grade eggs discarded by fertility clinics, and by obtaining human eggs through ovarian biopsy. We should also expect to see growing pressure to ease various state and institutional limitations on the sale of eggs for research.

Some more eccentric embryo research”such as the creation of human-animal hybrid embryos or the development of embryonic stem cells from earlier-stage embryos”is likely to see a serious decline in interest over the next few years. The purpose of these techniques was to overcome the shortage of human eggs for straightforward (non-cloning) embryo research and to sidestep the political pressure and ethical concerns raised by the destruction of embryos for research. Both sets of problems are significantly alleviated by the development of iPS cells (and, it must be added, the political pressure is alleviated by the election of a Democratic president). It is likely, therefore, that the attempts to produce human-animal hybrid embryos (which we know have been tried in China and Great Britain) will be scaled back. Attempts to find new ways to derive cells from human embryos will be limited as well. We can, however, expect continuing efforts to extend the period of gestation of human embryos outside the body”as more developed embryos and fetuses yield more useful cells and tissues.

Another set of emerging techniques, which would employ pluripotent stem cells to produce human eggs and sperm, are likely to develop swiftly in the next few years. These techniques would allow for manipulations of human reproduction to permit, for instance, homosexual couples to reproduce biologically (using, say, an egg from one female, then transforming the skin cells of another female into sperm cells with her genetic characteristics, and then producing an embryo by in-vitro fertilization). These techniques are almost certainly already possible with existing iPS techniques, though the efficiency involved would be quite low and the expense quite high. They will improve dramatically in the coming years.

As a result of all this, the likely scientific developments over the next few years move in two opposed directions: On the one hand, techniques to produce pluripotent stem cells without the need for embryos will certainly take center stage, reducing the volume of embryo destruction. On the other hand, successful human cloning for research is very likely, and we will see growing pressure to make more eggs available for research.

With regard to actual medical advancement, it is important to take note of the changed tone of expectations. Researchers now speak far less frequently of actual direct-cell therapies for particular diseases and conditions, because the lessons of animal research (and some implications of human adult stem-cell research) in recent years suggest that direct delivery of cells into the body of a patient will always carry grave risks of mutation and cancer. Moreover, they will also always remain extremely difficult to scale up to levels that would be required for treatment of widespread diseases or conditions.

Cell biology is instead increasingly directed to the study of small molecules that may be used to manipulate the development of cells through gene activation. It seems more and more likely that the most significant findings of the stem-cell revolution will involve ways of altering existing adult cells in the body rather than replacing lost or damaged cells. This suggests a far less prominent role for human embryos in this field of biology in the long run, but it also suggests a continuing interest in the detailed study of human development in the short run, which does involve the use and destruction of embryos. The public argument that stem cells from embryos will themselves be used to treat sick patients, however, is becoming increasingly untenable and untethered from the work of actual researchers in the field.

As far as public policy in the United States goes, the effort to enact limits on the destruction of human embryos for research (and on other unethical practices at the margins of cell biology) have yielded some modest but important achievements. All of these are now at risk, and some are quite certain to be overturned.

In 2001, President Bush permitted, for the first time, some limited federal funding of human embryonic stem-cell research, but under rules that denied funding to the use of any newly created lines of cells”thus avoiding a federally funded incentive for the ongoing destruction of human embryos. Congress twice passed bills to overturn these limits and allow for funding of newly created lines, and Bush twice vetoed the measures.

During the 2008 campaign, President Obama committed to overturning the Bush policy, and he will certainly do so. The particular character of the new policy will make some difference: It could, for instance, involve parental-consent requirements that might constrain its scope somewhat. But federal support for the use of cells from destroyed embryos will certainly grow significantly.

At this point, such support could fund only the use of cells from embryos but not the actual process of destroying the embryos. The Dickey Amendment, attached to the federal budget since 1995, prohibits funding for work in which embryos are actually destroyed. The new Congress may choose to remove the Dickey Amendment in next year’s budget, allowing for essentially no restriction on federal funding for the destruction of human embryos.

Opponents of the amendment certainly have the votes to remove it, but they will need to judge whether there is sufficient demand in the scientific community to merit the political cost, which means that the pro-life movement needs to prepare its case on the Dickey amendment, to make plain that there would be a cost.

In 2004, Congress enacted a ban on the patenting of human embryos. This prohibition, known as the Weldon Amendment, prohibits the patent office from granting patents that encompass a human organism as a patented product. This both establishes the principle that human beings should not be treated as property and limits the appeal of some manipulations of human embryos for research. The Weldon Amendment was forcefully opposed by the lobbying arm of the biotechnology industry and by some advocates of embryo research, and it may well be at risk in the next budget process.

In 2006, Congress passed and Bush signed a prohibition on the use of tissues or organs from a human fetus who had been gestated for the purpose of producing such tissues or organs (a practice known as fetal farming). This prohibition, which is not just a budget amendment but a statutory ban, affecting both the private and the public sector, is not likely to be undone by the new Congress, as there is not sufficient pressure from researchers to reverse it, and a reversal would be extremely unpopular.

These are, more or less, the only existing protections in federal law. There is no limitation on human cloning at the federal level, no prohibition on human-animal hybrid work or similar techniques, and no restriction on the use, procurement, or purchase of human eggs for research.

In the past, when Republicans have proposed to prohibit human cloning, the Democrats advanced a measure they described as a cloning ban, though, in fact, it would have prohibited only the transfer of a cloned human embryo to a womb for development to birth. The Democrats might pursue such a measure as a preventative step in this new Congress, but, since current law places no restrictions whatsoever on cloning, they may more likely see it as a needless effort and leave things as they are.

The only real opportunity for some positive achievement (rather than successful defense) in the next few years”and even this is a long shot”involves the question of egg procurement for embryo research. We are very likely to see growing pressure from researchers to ease institutional and some state rules that limit their ability to pay for eggs and that constrain them from working closely with fertility clinics to obtain eggs. The egg issue raises some concerns for a small but potentially significant element on the left, and at this point the usual biotechnology and disease-group lobbyists have not made it a key focus of their efforts. It may be possible to form a bare majority for setting some modest boundaries on the sale or procurement of eggs for research.

The prospects on the embryo-research front in the coming years are grim. We will certainly see the Bush funding policy overturned, and we will likely see rolled back most of the other modest protections enacted through great and arduous effort over a decade and a half. The egg-procurement question presents the only plausible opportunity for progress, but the pro-life movement should not despair of defensive successes. The Dickey and Weldon Amendments both have determined opponents in the scientific community (and especially in the private biotechnology sector) but both have a decent chance of surviving if the political costs of eliminating them can be increased. The first budget cycle of the new Congress will be the most crucial and difficult test on both fronts.

Yuval Levin is the Hertog Fellow at the Ethics and Public Policy Center, where he directs the program on Bioethics and American Democracy.

Image by Science History Institute licensed via Creative Commons. Image cropped.