A tarnished gold standard

The last-ditch defence for experimenting with human embryonic stem cells is that they are a “gold standard” for stem cell research. Nonsense.

Heard much about human embryonic stem cell research lately? Whether or not embryos could be destroyed in the search for medical breakthroughs was one of the most controversial topics in the last US presidential election. It sparked bitter debates over the ethics of creating and dissecting nascent humans in Australia, Canada and the UK.

When he signed an executive decree authorising federal funding for it, President Barack Obama was hailed as the saviour of American science. “We will vigorously support scientists who pursue this research,” he said in March. “And we will aim for America to lead the world in the discoveries it one day may yield.”

But after all the political hoop-la, have you heard about great medical advances from embryonic stem cells (ESCs)?

You haven’t – but don’t feel left out. No one has. In fact, a former head of the National Institutes of Health, Bernadette Healy wrote in Newsweek that “embryonic stem cells are obsolete”.

What’s more, a good number of stem cell scientists quietly agree with her. The scientist who first isolated human ESCs, James Thompson, of the University of Wisconsin, no longer works with them. Nor does Ian Wilmut, the Scottish scientist who cloned Dolly the sheep.

In fact, only a few weeks before the President announced his decision, the worst news possible about ESCs emerged. Israeli scientists reported an extraordinary case in the journal PLoS Medicine. A shady clinic in the Ukraine had injected human embryonic stem cells into the spine of a young boy with the fatal neuromuscular disease ataxia telangiectasia. Four years later, instead of bringing about a miracle cure, these cells developed into multiple brain tumours.

This was a horrifying outcome for the child and his parents, but to scientists it came as no surprise. Embryonic stem cells are meant to multiply wildly and rapidly. In fact, the test for identifying genuine embryonic stem cells is to see whether they develop into tumours when they are injected into a mouse. Most of the brain-cudgelling of scientists working on ESCs is devoted to disciplining these unruly cells. They try to get them to follow a specific developmental pathway so that they will morph obediently into heart cells, kidney cells, brain cells, and so on.

The problem is, more than 10 years after human embryonic stem cells were first isolated, this is still proving difficult. A single rogue cell amongst a million brain cells derived from ESCs could become a tumour.

And there is another problem for clinical applications of ESCs. Unless they have the same genetic complement as the patient, they will be rejected. Yet the potential stem cell therapies from ESCs will not have exactly the same genetic material and the foreign material could scupper the cure.

That’s one important reason why nearly all the clinical progress and research progress has been taking place in the labs of scientists who are working on adult stem cells and a new star performer, induced pluripotent stem (iPS) cells. These cells are isolated from a patient’s own tissue and have the same genetic make-up. They won’t be rejected. Nor will using them involve serious ethical problems because no embryos are destroyed.

So, given that there are serious ethical problems involved in using stem cells whose origin is a destroyed human embryo and given that there are serious clinical hurdles in using them as cures, what justification can there possibly be for using them?

Ethically, there aren’t any. An embryo is still a human being. We were all embryos once. If you know what you are looking at under a microscope, an embryo is recognisably human – a human being who is just a couple of days old. Sure, it is smaller than a pinhead – but according to the Big Bang theory, the whole universe was once smaller than a pinhead. Humanity is not proportional to size.

The problem is that many scientists are not about to surrender their right to do whatever research they see fit. They want to be the only judge of what is acceptable research, especially when it is something as fascinating as the origin of human life. 

Now that the potential of ESCs for curing is fading fast, they have a last line of defence against their critics. This is that human embryonic stem cells are the “gold standard of pluripotency”. In other words, they are essential for proving that rival types of stem cells are truly stem cells.

Harvard’s Professor George Daly, for instance, told the US Congress last year that “Embryonic stem cells remain the gold standard today and will remain so for the foreseeable future. If we are to maximize the pace of scientific discovery and accelerate development of new treatments for disease, we must continue to vigorously pursue all forms of stem cell research.”

Whenever it is argued that adult stem cells and iPS cells are viable alternatives to ESCs, Daly -– who is currently president of the International Society for Stem Cell Research -- and his supporters sneer that they are not equivalent to their gold standard.

The mantra of the “gold standard” has also been picked up by the media. It’s catchy and comprehensible. The gold standard for cola is Coke; the gold standard for search is Google; the gold standard for golf is Tiger Woods. And the gold standard for stem cells must be embryonic stem cells.

But it isn’t.

What exactly do these scientists mean by a “gold standard” for stem cells? Gold standard in what respect? A standard works only if you are comparing apples with apples and oranges with oranges.

If scientists obtain ESCs from surplus embryos in an IVF clinic, in what respect can you compare them to iPS cells? The former is not genetically compatible with a patient and the latter is. One was created in a relatively natural way by the union of sperm with an ovum. The other was created by marinading a skin cell in hormones and tweaking key genes – a very artificial process. What would they even hope to learn by comparing the two? From a medical point of view, you would be comparing apples with oranges.

Another source of embryonic stem cells is cloning, or nuclear transfer, as it is technically called. This might be deemed a relevant comparison, because both the cloned cells and the iPS cells have been exposed to the very strong likelihood of epigenetic changes because of the effects of the manipulations on genetic reprogramming. In other words, even if the genetic complement is identical, different ways of tweaking the cell can cause the genes to act differently.

For stem cell scientists, that sounds like a plausible comparison. But remarkably, despite all the hype, no one has ever obtained human embryonic stem cells by nuclear transfer. There have been announcements that human embryos had been cloned and that stem cells had been extracted from them. But the most ballyhoo-ed of these, in Korea, turned out to be an appalling, calculated fraud. Up to now, cloning, or nuclear transfer, has been a complete failure. 

The upshot of all this is that there is only one apple – induced pluripotent stem cells. The other apple, patient – specific human embryonic stem cells, doesn’t exist. On the other hand the two apples of mouse origin are available and could easily be compared.

They could be, but they haven’t. Astonishingly, no one has ever done this obvious experiment. Why? Because, in their eagerness to be first-est with the most-est in the race for miracle cures and Nobel prizes, scientists in the field have leap-frogged the usual sequence of experiments and rushed straight into work on human embryos. So if they have failed to show that the “gold standard” exists for mouse cells, how can they brazenly assert that it is necessary for human cells?

This is why the “gold standard” justification for continued work with human embryonic cells is simply not credible.

Michael Cook is editor of MercatorNet.