The Higher The Climb, The Bigger The Fall

by The Center for Bioethics and Culture on February 4, 2009

A seismic shift has occurred this week. For the first time ever in history, human embryonic stem cells will be injected into human subjects. Geron Corporation has enthusiastically announced the FDA’s approval of their Phase 1 clinical trial to begin using human embryonic stem cells in patients with new spinal cord injuries. This news came as no big surprise; Geron’s CEO, Thomas Okarma, has been promising for years that they would be the first in human trials using embryonic stem cells. Geron has poured some $100 million into embryonic stem cell research since 1996; they have much at stake as they begin this trial, injecting human embryonic stem cells into patients. I imagine investors in Geron stock are delighted now as its price soared some 50% with this news, and Geron stock has moved from “hold” to “buy” status. We shall see.

From Geron’s news release:

“Geron plans to initiate a Phase I multi-center trial that is designed to establish the safety of GRNOPC1 in patients with “complete” American Spinal Injury Association (ASIA) grade A subacute thoracic spinal cord injuries.”

Geron will recruit patients who have “documented evidence of functionally complete spinal cord injury with a neurological level of T3 to T10 and agree to have GRNOPC1 injected into their lesion site 7-14 days after their spinal cord injury.” They hope to begin their study as early as this summer.

While the world watches and waits as Geron begins this clinical trial, let me point out a rather significant statistic that most people don’t know. The majority of Phase 1 clinical trials fail, and they fail pretty miserably. Keeping this in mind, the scientific world should be watching even closer as Geron begins recruiting patients and the actual clinical trial unfolds.

How’s this for a statistic:

“In clinical trials, teams of physicians carry out studies designed to determine if the drug is safe in people and is an effective treatment for the disease in question. Of the 250 compounds that enter preclinical testing, only five will make it this far.”

Sources I spoke with tell me that the Phase 1 failure rate is 60%-90% and even as high as 95% with cancer drugs. So, the majority of new drugs in the Phase 1 trial, where safety is the primary focus, fail. If the drug is deemed safe, then it is permitted to move on to Phase 2 of the trial. With this kind of failure rate, you can quickly understand why the FDA takes safety in human clinical trials so seriously and why it is so very expensive to move a new drug or therapy onto the market.

Historically the biotech-cures-all approach to medicine is full of stops and starts, hype and hope, and disastrous results, therefore those in the scientific community who have pinned everything on embryonic stem cells being the holy grail – the gold standard against which all other research will be measured – and holding the secret of cures (remember, that is what this is all about), will be watching and holding their breath, hoping that Geron doesn’t fail. Art Caplan, director of the University of Pennsylvania’s Bioethics Center said, “It is going to take years to develop therapies” and we shouldn’t give patients false hope.

So very much is at stake for those of us who oppose embryonic stem cell research. While we hope that the patients who enter into this clinical trial are not further harmed, we also hope that embryonic stem cells don’t work because we object to using nascent human life instrumentally, no matter what good can be achieved. And if embryonic stem cells are successful in providing benefit to patients, it will be close to impossible to turn back the clock. This is a watershed moment.

Since Phase 1 trials focus primarily on safety, you can be sure that there will be a very strict and stringent protocol that will need to be followed, and at any given moment the trial could be stopped. This, of course, would be the kind of result that should significantly hinder any future studies using human embryonic stem cells in human subjects. The scientific community has placed so much hope in this area of research. But one wrong move and it all comes to an end. That’s reason to be nervous.

Two examples of safety concerns quickly came to mind when I heard of Geron’s news:

  1. The failure of Fetal Tissue Transplantation, which came about right after President Clinton took office in 1993, as the cure-all for Parkinson’s disease.
  2. The disastrous gene-therapy news of Jesse Gelsinger in 1993.

For all the hope and hype over fetal tissue transplants, the research has provided mixed results at best, and certainly the 15 years of research has not proved to be beneficial to patients. And the sad story of Jesse Gelsinger set gene therapy back decades. Can you say GM foods and Monsanto or e. coli and spinach?

Jennifer Couzin wrote a good article in Science titled, “Celebration and Concern Over U.S. Trial of Embryonic Stem Cells.” One chilling quote comes from John Gearhart, one of the leaders who first isolated embryonic stem cells back in 1998. Gearhart said, “We’re still a long way from really understanding a good deal about these cells and how to use them safely.”

So with massively high failure rates in clinical trials, the experts in embryonic stem cell research reminding us how little we still know about these cells and their safety and efficacy, along with the massive breach in the unethical use of human subjects in research (yes, I do believe the human embryo is a human subject) and progress in iPSC and adult stem cell research, we should all pause at this moment in time and ask ourselves do we want to set ourselves up for such a huge fall?

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