Paula Hammond: A new superweapon in the fight against cancer @ TED Talks Live

TED Talks Live were held at The Town Hall Theater in NYC, in November of 2015. I had the pleasure of attending all six nights to hear speakers present impactful Ideas Worth Spreading. This post is an analysis of a talk by Paula Hammond on how science is developing new techniques for battling the most aggressive and tricky forms of cancer.

Watch Paula’s TED Talk. Notice how she narrows the focus of her story to just a subset of cancers that are the most difficult to treat, then masterfully describes the problem, the solution, and the results of these new treatments.

Transcript

(my notes in red)

Cancer affects all of us — especially the ones that come back over and over again, the highly invasive and drug-resistant ones, the ones that defy medical treatment, even when we throw our best drugs at them. Engineering at the molecular level, working at the smallest of scales, can provide exciting new ways to fight the most aggressive forms of cancer.

Paula’s opening phrase, that ‘Cancer affects all of us’, is powerful in that it speaks to a disease we all know about, but I wish she had continued with something along the lines of, ‘While not everyone gets cancer, most everyone knows someone – friend, relative, co-worker – who has dealt with it.’ That would have been a much better way to expand on the narrative thread.

The balance of her opening establishes the context of her story as she speaks about the most challenging forms of cancer and a strategy of working at the molecular level to address them.

Cancer is a very clever disease. There are some forms of cancer, which, fortunately, we’ve learned how to address relatively well with known and established drugs and surgery. But there are some forms of cancer that don’t respond to these approaches, and the tumor survives or comes back, even after an onslaught of drugs.

Paula’s slide helps to illustrate the broad range of cancers, and the fact that while therapies have been developed to address some types, others do remain resistant to those therapies. She doesn’t need to list them off, the slide provides that information to the audience.

We can think of these very aggressive forms of cancer as kind of supervillains in a comic book. They’re clever, they’re adaptable, and they’re very good at staying alive. And, like most supervillains these days, their superpowers come from a genetic mutation. The genes that are modified inside these tumor cells can enable and encode for new and unimagined modes of survival, allowing the cancer cell to live through even our best chemotherapy treatments.

Using the term ‘supervillains’ is an appropriate analogy to describe how powerful and crafty these cancers are, and how difficult it is to defeat them. In this case, their craftiness comes from ‘a genetic mutation’, and to explain that term, Paula describes how the process works using language that the general public can better understand. This is something to keep in mind if your story contains terminology (on any topic) that your audience may not fully grasp when they hear it. Think about how you can explain what the term means in simpler words.

One example is a trick in which a gene allows a cell, even as the drug approaches the cell, to push the drug out, before the drug can have any effect. Imagine — the cell effectively spits out the drug. This is just one example of the many genetic tricks in the bag of our supervillain, cancer. All due to mutant genes.

While such mutations may manifest in many ways, Paula cites one example to illustrate her point. In a longer talk, 2 or 3 examples could be cited in order to paint a more detailed and diverse picture of the problem, but even this one example underscores the concept of cancer’s trickery. Identifying multiple story blocks will give you the option to expand or contract the length of your story.

So, we have a supervillain with incredible superpowers. And we need a new and powerful mode of attack. Actually, we can turn off a gene. The key is a set of molecules known as siRNA. siRNA are short sequences of genetic code that guide a cell to block a certain gene. Each siRNA molecule can turn off a specific gene inside the cell. For many years since its discovery, scientists have been very excited about how we can apply these gene blockers in medicine.

Once again, a technical term – siRNA – is simply explained and connected to the previous passage. A gene causes the problem, this approach blocks the gene. Easy to understand.

Paula then says, ‘For many years since its discovery…’, which is general in nature and keeps the focus of the sentence on the fact that scientists have been excited about the possibilities.

An alternative approach would have been to specify the year of discovery and/or name the scientists who made the discovery. That would add a sense of historical perspective and give credit to those who pioneered the technology. In the end it’s up to the speaker to determine how that statement will be worded. Something to consider when crafting your narrative.

But, there is a problem. siRNA works well inside the cell. But if it gets exposed to the enzymes that reside in our bloodstream or our tissues, it degrades within seconds. It has to be packaged, protected through its journey through the body on its way to the final target inside the cancer cell.

Some solutions are straightforward and easy to implement, but often times there’s a catch, a challenge that prevents the solution to work as intended. The use of words such as ‘exposed’, ‘degrades’, ‘packaged’, and ‘protected’ are common, nontechnical terms that clearly explain the problem and resolution.

So, here’s our strategy. First, we’ll dose the cancer cell with siRNA, the gene blocker, and silence those survival genes, and then we’ll whop it with a chemo drug. But how do we carry that out? Using molecular engineering, we can actually design a superweapon that can travel through the bloodstream. It has to be tiny enough to get through the bloodstream, it’s got to be small enough to penetrate the tumor tissue, and it’s got to be tiny enough to be taken up inside the cancer cell. To do this job well, it has to be about one one-hundredth the size of a human hair.

Paula’s use of ‘supervillain’, ‘superpower’, and ‘superweapon’, creates an alliteration of sorts (please correct me if you have a better grammar definition) that takes the listener from the ‘villain’ to ‘weapon’ via ‘power’.

Let’s take a closer look at how we can build this nanoparticle. First, let’s start with the nanoparticle core. It’s a tiny capsule that contains the chemotherapy drug. This is the poison that will actually end the tumor cell’s life. Around this core, we’ll wrap a very thin, nanometers-thin blanket of siRNA. This is our gene blocker. Because siRNA is strongly negatively charged, we can protect it with a nice, protective layer of positively charged polymer. The two oppositely charged molecules stick together through charge attraction, and that provides us with a protective layer that prevents the siRNA from degrading in the bloodstream. We’re almost done.

In the previous passage Paula explains what the solution has to do, and in this passage she talks about how that was actually done. Think about these three steps – this is what the problem looked like, this is what the solution needs to look like, and this is how that solution was created. This is a beautiful way to present a technical story to a nontechnical audience.

But there is one more big obstacle we have to think about. In fact, it may be the biggest obstacle of all. How do we deploy this superweapon? I mean, every good weapon needs to be targeted, we have to target this superweapon to the supervillain cells that reside in the tumor.

But our bodies have a natural immune-defense system: cells that reside in the bloodstream and pick out things that don’t belong, so that it can destroy or eliminate them. And guess what? Our nanoparticle is considered a foreign object. We have to sneak our nanoparticle past the tumor defense system. We have to get it past this mechanism of getting rid of the foreign object by disguising it.

So we add one more negatively charged layer around this nanoparticle, which serves two purposes. First, this outer layer is one of the naturally charged, highly hydrated polysaccharides that resides in our body. It creates a cloud of water molecules around the nanoparticle that gives us an invisibility cloaking effect. This invisibility cloak allows the nanoparticle to travel through the bloodstream long and far enough to reach the tumor, without getting eliminated by the body.

On one level we know this process is highly complex, but using ‘a cloud of water molecules’ to provide an ‘invisibility cloak’ is all we need. We understand the concept of using a disguise to avoid detection.

Second, this layer contains molecules which bind specifically to our tumor cell. Once bound, the cancer cell takes up the nanoparticle, and now we have our nanoparticle inside the cancer cell and ready to deploy. Alright! I feel the same way. Let’s go!

Paula is so clear in describing the problem and solution she’s dealing with that the audience gets excited and cheers. They can sense victory. This is no easy task, but if your story involves a problem / solution scenario, think about how you can build up a sense of anticipation and accomplishment within your narrative.

The siRNA is deployed first. It acts for hours, giving enough time to silence and block those survival genes. We have now disabled those genetic superpowers. What remains is a cancer cell with no special defenses. Then, the chemotherapy drug comes out of the core and destroys the tumor cell cleanly and efficiently. With sufficient gene blockers, we can address many different kinds of mutations, allowing the chance to sweep out tumors, without leaving behind any bad guys.

So, how does our strategy work? We’ve tested these nanostructure particles in animals using a highly aggressive form of triple-negative breast cancer. This triple-negative breast cancer exhibits the gene that spits out cancer drug as soon as it is delivered. Usually, doxorubicin — let’s call it “dox” — is the cancer drug that is the first line of treatment for breast cancer. So, we first treated our animals with a dox core, dox only. The tumor slowed their rate of growth, but they still grew rapidly, doubling in size over a period of two weeks.

Then, we tried our combination superweapon. A nanolayer particle with siRNA against the chemo pump, plus, we have the dox in the core. And look — we found that not only did the tumors stop growing, they actually decreased in size and were eliminated in some cases. The tumors were actually regressing.

Once a solution has been architected, it must be deployed, else it’s just a theory. In this passage, which is just over a minute, Paula provides a specific case where the solution was used. Note how she delivers the final sentence – ‘The tumors were actually regressing.’ – her pace slows as she clearly enunciates each word, one at a time. We feel the importance of her words and understand the impact that her solution had on the cancer.

What’s great about this approach is that it can be personalized. We can add many different layers of siRNA to address different mutations and tumor defense mechanisms. And we can put different drugs into the nanoparticle core. As doctors learn how to test patients and understand certain tumor genetic types, they can help us determine which patients can benefit from this strategy and which gene blockers we can use.

Ovarian cancer strikes a special chord with me. It is a very aggressive cancer, in part because it’s discovered at very late stages, when it’s highly advanced and there are a number of genetic mutations. After the first round of chemotherapy, this cancer comes back for 75 percent of patients. And it usually comes back in a drug-resistant form. High-grade ovarian cancer is one of the biggest supervillains out there. And we’re now directing our superweapon toward its defeat.

As a researcher, I usually don’t get to work with patients. But I recently met a mother who is an ovarian cancer survivor, Mimi, and her daughter, Paige. I was deeply inspired by the optimism and strength that both mother and daughter displayed and by their story of courage and support. At this event, we spoke about the different technologies directed at cancer. And Mimi was in tears as she explained how learning about these efforts gives her hope for future generations, including her own daughter. This really touched me. It’s not just about building really elegant science. It’s about changing people’s lives. It’s about understanding the power of engineering on the scale of molecules.

A key aspect of the Ideation phase is to identify why your story matters to those who will be listening, watching or reading. Paula does just that as she uses a story block about another person – in this instance two people, the mother and daughter – to bring home the message that ‘engineering on the scale of molecules’ has such far reaching effects, and may very well touch those in the audience.

I know that as students like Paige move forward in their careers, they’ll open new possibilities in addressing some of the big health problems in the world — including ovarian cancer, neurological disorders, infectious disease — just as chemical engineering has found a way to open doors for me, and has provided a way of engineering on the tiniest scale, that of molecules, to heal on the human scale.

In conclusion, Paula provides three examples – varian cancer, neurological disorders, and infectious disease – where this technology may deliver promising solutions. She brilliantly ends with a connection between ‘tiniest scale’ and ‘human scale’.

I encourage you to watch this talk a second time. Pay attention to how every word matters, and how she constructs the problem / solution storyline. Despite the complexity of her topic, we are never lost or confused. In similar fashion, your story should ideally take people on a journey without any bumps along the way.

Thank you.

[Note: all comments inserted into this transcript are my opinions, not those of the speaker, the TED organization, nor anyone else on the planet. In my view, each story is unique, as is every interpretation of that story. The sole purpose of these analytical posts is to inspire a storyteller to become a storylistener, and in doing so, make their stories more impactful.]

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