My mom has Alzheimer's Disease.

And it's not getting any better.

No, it hasn't gotten THAT much worse. She's 82 and she's still driving.

Still has her independence.

Mostly.

But I'm nervous.

When am I gonna get the call?

That she's lost. And can't find her way home. Assuming she even thinks — or knows — to call me.

Part of the reason she's doing as well as she IS, I'm convinced, is because of the Alzheimer's drugs and treatments that were available.

Thank GOD for Aricept.

I was QUITE nervous five years ago or so, when my mom experienced a significant, downwards lurch. She was only 77 and in quite good health, for her age.

And she was slipping.

QUICKLY.

And then she went on Aricept and it stabilized things, if not gave her a bit of a BOUNCE.

THANK YOU Eisai Pharmaceuticals.

But now, after five years, Aricept seems to have stopped working. And my mom's starting to slip again. And there's no next Alzheimer's drug to try.

Not one I TRUST.

Yes, there IS Aduhelm, the brand name for Biogen's newly approved compound, Aducanumab. But, even AFTER a recent price cut, Aduhelm still costs as much as a CAR — per YEAR — and, worse, it's debatable whether Aduhelm even WORKS.

Because, I'd suggest, Aduhelm doesn't make SENSE.

Because the Amyloid HYPOTHESIS doesn't make sense.

As Ted Williams said, "There's this thing called logic..."

Demonstrated, in part, by Biogen's having to unleash the tools of Confirmation Bias — Data Dredging, P-Hacking, and everything — to turn what's only the most RECENT failed study into something minimally positive. The torturous, if not FRAUDULENT, efforts to sculpt and polish something of beauty out of what, increasingly, looks like a turd.

Because Aduhelm MAY — and, if I'm right, WILL — make things WORSE and not BETTER. Not just in terms of ARIA, and brain swelling and bleeds, which are bad ENOUGH, but, I fear, by interfering with a NECESSARY and important process in the brain.

The brain's response to infection.

Part of its immune response.

And this podcast is my attempt to try to figure out what the HELL happened.

How DID that happen?

With Alzheimer's Disease research, in particular.

How DOES that happen?

With Innovation in GENERAL.

And what can be DONE about it.

Starting off with the question of how the Alzheimer's Disease industry has accomplished so LITTLE.

Basically nothing.

At BEST.

It's failed to produce a successor to Aricept and, and DESPITE, spending — and WASTING — at least 20 years and billions of dollars on Aducanumab. And all the other Amyloid clearing compounds.

And the Amyloid Hypothesis, in general.

How does THAT happen?

But, of course, The Innovation Podcast is about MORE than just Alzheimer's Disease. Alzheimer's Disease is just a case study.

A sandbox.

A starting point.

The mistakes made, and questions raised, by the disaster that is Alzheimer's Disease research...

• Begley: How an Alzheimer's Cabal...

...starting with how the Amyloid Hypothesis came to dominate the field, to the exclusion of EVERYTHING else, apply to the WHOLE of Innovation.

Not just what HAPPENED, but what HAPPENS.

And why and how.

What gets would-be innovators OFF track?

And how do you keep them ON track?

How do you FACILITATE the good stuff? And PREVENT the bad stuff?

How do you help improve the process and pace of Innovation?

And then, once you've got an Innovation that actually works — or, better yet, BEFORE — how do you deal with the problem of Change?

And people's natural resistance to Change.

How do you make the act of Innovating — from problem to idea to product or service — BETTER?

And help my mom?

Or, at least, because it's likely too late for HER, people LIKE her.

Which — because I'm so much LIKE my mom, such that we seem to share the same kind of BRAIN — includes me.

Trailer: The Innovation Podcast

This is The Innovation Podcast, a practical, all about the HOW, discussion of Innovation, Entrepreneurship, and the intersection of the two, which I call Innopreneurship, as well as Innovation's evil twin, Unnovation.

Other topics of interest to me include New Products and Services, Science and Scientific Discovery, Paradigms, Crisis, Change, Reality, Creativity, and Critical Thinking.

While doing so runs COUNTER to the Conventional wisdom — which, too often, tells people to focus only on the POSITIVE — I've decided to start out The Innovation Podcast discussing Alzheimer's Disease research, a field which, I've found, is a complete and utter disaster.

Spectacularly UN-novative.

Because it's rife with failures to question long-held assumptions.

To THINK.

And is a treasure trove, as a result.

DR. KARL HERRUP: People discovered — after they looked at enough samples from brains of people who had died with totally normal cognition — they discovered that almost 30% of them had deposits of amyloid and tau that would be perfectly consistent with a diagnosis of Alzheimer's disease, if it were given to a pathologist who was unaware of the diagnosis.

That observation, when it came out, was my first red flag and started my thinking that, "Well wait a minute, if 30% of NORMAL people have the same deposits that are supposed to CAUSE Alzheimer's disease, there's something wrong here."

CHRIS O'LEARY: In (Thomas) Kuhn's terms, that's the Anomaly.

DR. HERRUP: I accept that completely. Because that's exactly what it is. And it's the core Anomaly, I think, in our field...

I remember, it was almost a decade later, that I (first) allowed myself to think, "Well, gee, let us think about Alzheimer's without amyloid." And I know that sounds crazy. But the point I'm trying to make is that the power of Groupthink is that even for someone who would recognize that there were problems, the Groupthink is so strong, and the desire to work in the Alzheimer field was obviously strong in me — I wanted to find a solution — I couldn't let go of Amyloid, even though I knew it had its weaknesses.

Red flags.

Anomalies.

The power of Groupthink.

While the book The Secret, and similar works of New Age mysticism, would tell you that focusing on a disaster like Alzheimer's Disease research is a BAD idea, and would have you focus elsewhere — on something more POSITIVE — I've found GOLD in those stories.

In what Thomas Kuhn, the Paradigms guy, describes as Crisis.

In dysfunction.

Secrets that help explain when and why Innovation HAPPENS.

And DOESN'T.

Which, if you're paying attention, will tell you what you need to do if you want to ensure it DOES.

DR. RUTH ITZHAKI: In the case of Alzheimer's Disease, it's about 60 percent — 50 to 60 percent — of people with Alzheimer's Disease, we think, who have this combined factor of virus in the brain and this genetic factor.

At first there was a great deal of interest, but then it sort of dwindled, and for all the years after that — which led to a paper in The Lancet, which was quite pleasing — we had to fight huge battles to get money and to get papers published. And, of course, one depends on the other. You can't get grants and funding if you haven't published papers. If you can't persuade people that what you're saying is factual, and likely correct, you don't get any funds. So it was a very, very difficult situation. I had to beg borrow, normal steal to get money, or, more likely I relied on small organizations. We're more willing to take the risk to do novel work, small funding bodies rather, rather than the large funding bodies, who just wouldn't look at it.

Shunning.

A refusal to consider alternatives.

And acknowledging that can be a problem, even in the — all too human — enterprise that is science.

A problem that, once — but ONLY once — acknowledged can be addressed and solved.

That, and NOT Brainstorming or Thinking Outside the Box or all the other things the Conventional Wisdom, and the Creativity gurus, tell you to focus on, is where I've learned to look for the HOW of Innovation.

An insight which, to my frustration, I first glimpsed, on my own, thirty years ago, in the Summer before grad school. And abandoned because it wasn't what the Conventional Wisdom told me was the "right" answer.

The "correct" way to go about things.

Because it's too negative.

Among other things.

But, thanks to a conversation with someone who'd actually DONE Innovation, I was led BACK to it, twenty years ago. And in the prior years. In critical conversations with Pat Sullivan, the creator of ACT! and the entire Contact Manager product category, Pat told me HOW he did it...

I had no intention of creating ACT!

I was a computer salesman. Selling computers every day. Selling Lotus 1-2-3 and dBase and software along with it.

I had, in the process of selling, lots of problems.

I had pain.

That's the best way to say it.

I've used the lesson I first figured out on my own — reinforced by my experience working for and with, and talking to, at length, Pat Sullivan — to start my own entrepreneurial ventures.

And make my own scientific discoveries.

In the process, I've seen, for myself, when and why and how change — and thus Innovation — happens.

And doesn't.

Which enables me to have very DIFFERENT conversations with people.

Because I'm looking for fundamentally different THINGS.

Things the Conventional Wisdom about Innovation not only doesn't LOOK for but, problematically, and too often, tells you to IGNORE.

Which is the root of MY, and I suspect YOUR — because you're still listening — frustration.

And what I'm trying to do, with The Innovation Podcast, is offer an alternative way of thinking about Innovation.

How to DO it.

And how to SEE it.

Opportunity.

An approach that, first and foremost, is focused on what successful innovators DO — actually — and not the Conventional Wisdom.

If these are the kinds of topics and questions that interest you, then I'd encourage you to LISTEN, and maybe even SUBSCRIBE, to The Innovation Podcast, which is available through most of the major podcast providers, including Apple Podcasts, Spotify, and Anchor.

Thanks, and I'm excited to see where this thing goes.