October 31, 2020

The Niche

Knoepfler lab stem cell blog

How iPS cells germinated in part in Seattle in the 1980s

What if I told you I believe that iPS cells really began in Seattle in the 1980s? 

Call me crazy?

Read on.

We hear a lot about how iPS cells were first created in 2006 in Japan by Shinya Yamanaka.

I often say this myself.

However, as is the case with so much in science, the story is not that simple. For example, while Till & McCulloch are often unambiguously called the discoverers of stem cells, I pointed out in an earlier post “Who really discovered stem cells?” how before these amazing scientists were even born, previous generations of amazing scientists were already studying stem cells.

I did a post this week on my top 10 list of iPS cell papers and quite a few people have remarked that 3 of the papers on the list precede 2006 and don’t mention iPS cells in any shape or form.

What the heck?

Let me explain.

There was a scientist named Harold (Hal) Weintraub at a place called the Fred Hutchinson Cancer Research Center (or as many of us call it affectionately for short “The Hutch”) in Seattle. You can read more about him here on the Hutch website.

Hal WeintraubHal was definitely one of a kind and in a good way. I only met him once when I was a grad student at UCSD and had gone up to the Hutch to give a talk. I did not know him well, but when I did my postdoc at the Hutch I became very good friends with those who had known him well and without exaggeration I can say they loved the guy. I also knew Hal’s science well and was a big fan.

When I arrived at the Hutch in Bob Eisenman’s lab to start my postdoc in 1998, people were still grieving Hal’s death 3 years earlier (see his NYT obit here). I also remember the moment I gave the sad news to my doctoral advisor, Mark Kamps, that Hal had passed away. For the first time in my years of working with Mark, he was visibly shaken. He thought the world of Hal and had interacted with him during a long running series of joint meetings between Hutch and Salk scientists called the “Salk-Seattle Meetings”, which sadly no longer take place.

Hal was a visionary researcher in the area of genes and cell fate. I am convinced he would have won the Nobel Prize and deservedly if he had not been taken from us by a brain tumor. At the same time Hal was the kind of scientist and person that I admire. He loved to talk science with his fellow scientists at all levels. He was creative and a deep thinker.

So, you might ask, why do I think Hal deserves some of the credit for the discovery of iPS cells?

Hal himself would never have asked for credit as he was a very modest person, but I believe credit is due.

Hal did pioneering studies of how genes influence cell fate. His models of how genes direct cell fate were exemplified by his lab’s seminal work on MyoD, a powerful transcription factor that can direct cell fate.


Hal’s lab’s first paper (see top portion above) reporting the existence of what would later be called “MyoD” for “MYOblast Determination gene” was truly revolutionary. His team reported the fact that introduction of a single defined factor, MyoD, induced fibroblasts into myoblasts that differentiate into myotubes. Sound familiar? In fact MyoD reprogrammed even non-fibroblastic lineage cells into the muscle lineage.

So in the late 1980s Hal demonstrated a defined factor could induce direct reprogramming of cell fate.


The Weintraub lab papers from 1987 and 1988 more fully fleshed out the MyoD story.

In a perspectives piece just printed a few days ago, Yamanaka himself also attributes some of the credit in the pre-history of iPS cells to Hal Weintraub and I admire Yamanaka for that.

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