GERON’S IND FOR SPINAL CORD INJURY PLACED ON HOLD

Geron Corporation has made a cell line called GRNOPC1 from embryonic stem cells. GRNOPC1 is an “oligodendrocyte precursor cell” or OPC line. Before you blow a gasket at the sight of such a long-winded description, just remember that nerves are like wires and wires need insulation.  OPCs are the cells that make the insulation.  During spinal cord injury, the insulation dies off and it causes nerves to malfunction.

In collaboration with Hans Keirstead at UC Irvine, Geron developed a protocol for the administration of GRNOPC1 cells to animals with acute spinal cord injuries. His protocol showed that the OPCs were safe (no tumors were seen, even after one year) and somewhat effective. Some scientists were skeptical, since the mice had somewhat less severe spinal cord injuries.  Nevertheless, Geron was granted an Investigational New Drug Application from the FDA to conduct a Phase I trial with their OPC cell line.

They apparently, however, have bit a bit of a snag. Here is a press release from Geron Corporation.

Geron Corporation today announced that its IND (Investigational New Drug application) for GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the FDA pending the agency’s review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial.

Since filing the IND, Geron has been undertaking studies to enable dose escalation of its spinal cord injury product, and has been investigating application of the product to other neurodegenerative diseases. The company has also been performing additional product characterization and conducting further animal studies. Data from this work has been submitted to the FDA. Geron will work closely with the FDA to facilitate their review of the new data and to release the clinical hold. No patients have yet been treated in this study.

From the sound of it, this hold is merely an administrative procedure that the FDA routinely undergoes when presented with new data.  However, if the new data is completely consonant with previous findings, why would there be a hold? We simply do not know at this time.  It is entirely possible that nothing is amiss, and this is merely FDA policy.  However, it is also possible that Geron’s new product does not behave exactly as they thought.

The development of the first cholesterol-lowering drug (lovastatin) experienced a slow-down when a related product being developed in Japan caused cancer in dogs. Roy Vagelos, president of Merck at the time, contacted the FDA and suspended all clinical trials. Further testing by Merck showed that this was an anomaly, and extensive clinical use has vindicated this finding. Maybe this is a similar situation for Geron’s OPC line?  Only time will tell.

Induced Pluripotent Stem Cells Pass A Major Test

Induced Pluripotent Stem Cells (iPSCs) show virtually all the same characteristics as embryonic stem cells manufactured by manipulating and destroying human embryos. The final test that these cells have yet to pass is whether or not they can fix a hamstrung embryo and allow it to develop into an adult made from the stem cells.

If embryonic stem (ES) cells can make any tissue in the adult body, then they should, when placed in an embryo, make any and all adult tissues. Furthermore, if placed in an embryo that cannot make adult structures, then the embryonic stem cells, if they are truly pluripotent, should take over and make the embryo. This type of test is called tetraploid complementation. It uses embryos that have four copies of each chromosome. Tetraploid embryos, those with four copies of each chromosome, can make the placenta, but not the embryo. Therefore, if embryonic stem cells are injected into tetraploid embryos, the embryos will not die. Instead the embryonic stem cells will respond to the new environment in which they were placed and make the embryonic, fetal, and adult structures. This experiment is tetraploid complementation and embryonic stem cells can do this. Can iPSCs do this? Recent data strongly argues that they can.

Qi Zhou at the Chinese Academy of Sciences in Beijing and his colleagues, Shaorong Gao at the National Institute of Biological Sciences in Beijing, and Kristin Baldwin of the Scripps Research Institute in San Diego, California, made iPSCs, injected them into tetraploid embryos, placed them into surrogate mother mice, and observed the birth of mouse pups that were genetically identical to the iPSCs that were injected into the tetraploid embryos.  When these mouse pups grow to maturity, they are also fertile.

These experiments show that iPSCs have they same ability to form all the tissues of the adult human body as embryonic stem cells made from the destruction of embryos.  In short we DO NOT NEED embryonic stem cells from from the corpses of human embryos to cure sick people.

Is the Embryo Like an Acorn Rather than an Oak Tree?

Michael Sandel is a professor of political theory at Harvard University and was a member of President George W. Bush’s President’s Council on Bioethics.

Sandel states that even though every oak tree was at one time in its life an acorn, “it does not follow that acorns are oak trees.” Why? Compare how we might regard the loss of a magnificent oak tree over the loss of a single acorn. While the loss of the oak tree is received with distress and disappointment, the loss of the acorn hardly evokes a response. The same kind of disparate response is evoked by the loss of a mature human being over the loss of a human embryo. Therefore just as an acorn is a different kind of thing from an oak tree, a human embryo is a different kind of thing than a mature human person.

This argument has a lot of things wrong with it. In the first place, it begins with a significant biological error. Acorns and oak trees are both oaks, that is, members of the genus Quercus. They are the same organism at different stages of development. Sandel acknowledges this at first, and then denies it based on features that the oak tree acquires later in its development.

Secondly. Robert George and Franciscan University of Stubenville philosopher Patrick Lee have pointed out that the characteristics Sandel uses to categorize oak trees and acorns into different groups, like grandeur, beauty and so on, are “accidental” attributes. This is just a fancy way of describing a feature that is incidental to who you are and not essential. You can change an accidental attribute of something without affecting what it is. A good example is skin color in humans. People can have red, yellow, black or white skin and still be people. If their skin color changes, like when they get a tan in the summer and lighten up in the winter, they are still people. Herein lies the whole reason why it was evil for people with lighter skin to enslave those who had darker skin. Even though some argued that people with dark skin were not human persons, this is plainly ridiculous because a person can have light or dark skin and still be a person – skin color is an accidental attribute. Thus, a scrawny, scruffy, diseased oak tree with twisted bark is just as much an oak tree as a large, grand one. The grandeur, size, and beauty of the tree are accidental features that do not make it an oak tree. Sandel has made accidental features of oak trees and humans the most important things about them even though they are not.

George and Lee make other telling points against Sandel’s analogy. If acorns are to embryos as oak trees are to people, then what about oak saplings? Forest managers often cull oak saplings to prevent excessive crowding of trees and promote the health of the forest, and no one has any misgivings about such a practice. Yet if acorns are like human embryos then oak saplings are like human toddlers. We would not entertain culling toddlers. We would also not have any trouble with pulling up and burning a diseased, disheveled oak tree, but killing the mentally or physically disabled would be just plain incorrigibly evil. Clearly, Sandel’s analogy simply does not work.

Finally, Sandel’s main point seems to pivot around how he feels about the embryo. According to Sandel an oak tree and acorn are not the same kind of thing because we feel much more strongly attached to an oak tree than to an acorn. This is revealed in Sandel’s statements that “more than half of all fertilized eggs either fail to implant or are otherwise lost,” and “the way we respond to the natural loss of embryos suggests that we do not regard this event as the moral or religious equivalent of the death of infants.” Sandel gets his facts wrong about the percentage of embryos that die, but his assertion that the lack of a funeral means that the embryo is not a human person is a troubling one. What is it about having a funeral after you die that makes you a person? Did people slaughtered by Saddam Hussein, Pol Pot, or Adolph Hitler and buried in mass graves have a funeral? Were they not human persons? Of course they were. The embryo normally dies before we know anything about it or have a chance to become attached to it. Just because we do not hold a funeral for its demise is neither here nor there.

I think Sandel’s ethic gets even more sinister if we take it to its logical conclusions. My daughter just returned from a mission trip to a homeless shelter in Minneapolis, Minnesota. While there, she and her friends encountered a homeless lady who was afflicted with bipolar disorder. Her parents lived four doors down from her daily haunt, but never came to even talk to her or invite her home. Previously, she was even in a coma for several weeks, but her parents never came to see her or gave the slightest indication that they cared about her condition. This homeless lady’s parents have completely abandoned their own daughter. They don’t like her mental illness. In short, they don’t “feel” like being her parents anymore. Under Sandel’s ethical criteria, what these parents did was morally fine. Yet any parent worth their moral salt will tell you that their children are ALWAYS their children, and this homeless lady’s parents have failed in their most basic duty to their own daughter. Such neglect is an outrage, but if we take Sandel seriously, this lady’s parents were morally upright in all they did. The consequences of Sandel’s treatment are heinous, unchristian and unworkable for any society.

In the end Sandel has offered a troubling recipe for justifying the destruction of embryos – because he does not feel a strong attachment toward them. Such thinking is not only unconvincing, but morally dangerous.