Preface

In 1996, I received a visit from two academic scientists. At that time, I was Director of Molecular Neuroscience at SmithKline Beecham Pharmaceuticals, and the visitors wanted to talk about stem cell therapies for brain disorders. The visitors were from the Institute of Psychiatry in London, and they came to me because they hoped SB might invest in their stem cell technology.

They had chosen an unfortunate moment. I had just been part of a company working party investigating stem cell therapies. Upper management had heard of innovations in stem cells, and some competitors were moving into the area, albeit in a small way. Management wanted to know if there was any realistic prospect that stem cells might be used to treat major disorders, such as diabetes, heart disease, or stroke. They wanted to know if there might be an investment opportunity for our company in cellular therapy.

Our working party had talked to top scientists in the field in both Europe and the United States. We’d been impressed with the people and the progress, but we recommended that SB stay out of cell therapy. I had recently appeared on BBC Radio 4’s Science Now to say that I couldn’t see a breakthrough in stem cell therapy in Parkinson’s disease—one of the main disorders under study—for at least five years. Much progress had been made, but I thought the challenges were still enormous. Furthermore, I had a strong suspicion that some researchers in the field, experts though they were, had underestimated the enormity of what they were trying to achieve.

I was trained as a developmental neurobiologist, and had been studying brain development for some years. Stem cell scientists were trying to make stem cells build new brain tissue, so they were trying to reproduce in the damaged brain what only normally happens during development. But brain development takes place in the very peculiar circumstances that occur only in the fetus, when the brain is much smaller and less complex. The idea that you could repeat the trick in the tangle of an aged brain seemed to me very unlikely—a bit like trying to walk across the modern City of London using the original 1875 Ordnance Survey map. Some of the routes would still be intact, but you would probably discover a few skyscrapers blocking your path.

So when I met my visitors—Jeffrey Grey and John Sinden—we talked back and forth for a while about what they were trying to achieve, until eventually they asked whether there was any chance that SB might be prepared to invest in their research. I said I doubted it. Why? asked Jeffrey. Because we don’t think it will work, I replied. Oh, but we’ve already shown that it does, said Jeffrey, and he proceeded to describe a series of experiments they had completed. What the data seemed to show was precisely what I thought was impossible. Experimental animals with damaged brains had been injected with stem cells. As a consequence, new brain cells had been produced and—most important—the animals got better. The stem cells had apparently aided recovery from brain damage.

Psychologists have a term for the conflicted sensation I experienced at this point. “Cognitive dissonance” describes the disorientation you feel when your basic beliefs and assumptions are undermined by demonstrable fact. I probably looked as uncomfortable as I felt. Being an astute professor of psychology, Jeffrey recognized the situation and gave me his cheekiest smile. How about five million pounds, he asked?

Jeffrey and John didn’t get their five million off SB, but the year after our meeting, together with another colleague, Helen Hodges, they formed a start-up company to commercialize their stem cell technology. The following year they asked me to join them, and I became a consultant to their new enterprise. Roughly a decade later, I helped them apply to the MHRA (Medicines and Healthcare products Regulatory Agency) for authorization to commence a clinical trial for a stem cell therapy in stroke. This became the “PISCES trial,” the first clinical trial in Europe of a stem cell therapy for a neurodegenerative condition.

Interest in stem cell therapies for brain disease has grown substantially over recent years. I am constantly contacted by patients, or more usually by relatives of patients, anxious for news of a successful therapy. I have contributed to conferences and working parties in diverse settings—the London School of Economics, the Nuffield Council on Bioethics, the Academy of Medical Sciences—and been struck by the interest of diverse professional groups in stem cells, from sociologists to ethicists, anthropologists, and lawyers, all eager to understand how stem cell therapies might impact their domains. The general public is no less engaged. One of the most exhilarating discussions I have had on brain therapies was following a lecture to the “University of the Third Age” in Cambridge. Mostly retirees, with enormous depth and breadth of knowledge and experience, this audience had a particular interest in diseases of the aged, and they wanted to understand precisely the prospects for effective therapy. The stimulus provided by these diverse interactions represents the impetus for this book.

What follows, though not a memoir, is in a sense a progress report on my state of cognitive dissonance. Will there be successful stem cell therapies for the brain or won’t there? If I was right about the likelihood of it working, how come Jeffrey’s mice got better? If he was right, what on earth could the stem cells be doing—and might they do the same for human patients? The answer, for those who don’t want to read to the end of the book, is that we were both right.