Susan Solomon: The promise of research with stem cells

Summary

The speaker discusses the transformative potential of stem cell research, highlighting its role in modeling diseases, understanding illness, and developing personalized medicine. They emphasize the need for new technologies and research models to bridge the gap between academic research and pharmaceutical development, ultimately aiming to revolutionize drug testing and treatment.

Takeaways

• 🌟 Embryonic stem cells are pluripotent, meaning they can develop into any cell type in the body, and are crucial for disease modeling and drug development.
• 🔬 Stem cell research is transforming our understanding of diseases and could lead to the development of more effective treatments and preventive measures.
• 💡 The New York Stem Cell Foundation Laboratory was established in 2005 to provide a safe haven for stem cell research, free from political and financial interference.
• 🤖 A new technology combining software and hardware has been developed to generate a diverse array of stem cell lines, essentially creating 'avatars' of humans for disease modeling and drug testing.
• 🧬 The potential of human genome sequencing is being realized through the use of stem cells, allowing for more personalized and effective clinical trials.
• 🧪 Induced pluripotent stem cells (iPS cells), derived from reprogrammed skin cells, offer a powerful tool for disease modeling and drug discovery, though they are not as versatile as embryonic stem cells.
• 🧬 A breakthrough in 2008 involved turning skin biopsies from ALS patients into motor neurons, providing the first model of a disease in living human cells.
• 💊 Current drug testing methods are inefficient and costly, with only 1% of tested drugs successfully making it to market, highlighting the need for better disease models and testing platforms.
• 👩‍🔬 The development of genetically diverse stem cell lines is essential for personalized medicine, allowing for more targeted and effective drug treatments based on individual genetic profiles.
• 🔎 The pharmaceutical industry needs to move away from a one-size-fits-all approach to drug development, considering the genetic diversity of the population to ensure safety and efficacy.
• 🏥 Automated robotic technology for stem cell production is set to revolutionize drug discovery, making the process more scalable, consistent, and personalized.

Q & A

What are embryonic stem cells and why are they significant for medical research?

Embryonic stem cells are pluripotent cells that have the potential to develop into any cell type in the human body. They are significant for medical research because they can be used to replace damaged or diseased cells and have the potential to revolutionize the understanding and treatment of various diseases.

How can stem cells be used to model diseases and contribute to drug development?

Stem cells can be used to create models of diseases by reprogramming them into the specific cell types affected by the disease. This allows researchers to study the disease process in a controlled environment, understand why cells become sick, and test potential drugs for effectiveness and safety.

What is the significance of induced pluripotent stem cells (iPS cells) in medical research?

iPS cells are a type of pluripotent stem cell derived from adult cells that have been reprogrammed to an embryonic-like state. They are significant because they can be generated from a patient's own cells, avoiding ethical issues associated with embryonic stem cells, and can be used for disease modeling and drug discovery.

What is the New York Stem Cell Foundation Laboratory and what was its purpose?

The New York Stem Cell Foundation Laboratory was established in 2005 to provide a private, safe haven for stem cell research. Its purpose was to advance stem cell research without political or financial interference and to bridge the gap between academic research and the development of drugs and treatments by the pharmaceutical industry.

What challenges did the speaker identify in the current system of drug development?

The speaker identified several challenges, including the long time frame (13 years on average), the high cost (4 billion dollars per drug), and the low success rate (only 1% of drugs make it to market). Additionally, current drug testing often relies on animal models, which may not accurately represent human diseases.

What is the concept of 'avatars of ourselves' in the context of stem cell research?

The concept of 'avatars of ourselves' refers to the use of genetically diverse stem cell lines that represent different individuals. These avatars can be used to conduct clinical trials in a dish with human cells, allowing for more personalized and effective drug development.

How does the speaker describe the potential impact of stem cell research on the future of disease treatment?

The speaker believes that stem cell research will lead to a future where major diseases like Alzheimer's and diabetes are viewed as preventable, similar to how polio is viewed today. This is due to the ability of stem cells to model diseases and contribute to the development of more effective and safer treatments.

What is the role of genetics in the development of personalized medicine using stem cells?

Genetics plays a crucial role in personalized medicine as it helps in understanding the individual differences in how diseases affect people and how they respond to treatments. By using stem cells from a genetically diverse array of individuals, researchers can develop drugs and treatments tailored to specific genetic profiles.

What was the issue with the drug Vioxx mentioned in the script, and how could stem cell technology have prevented it?

Vioxx was a drug that helped alleviate severe arthritis pain but caused severe and sometimes fatal heart side effects in some patients. Stem cell technology could have prevented this by allowing for testing on a genetically diverse array of cardiac cells, identifying which genetic profiles would be affected by the side effects and thus preventing the drug from being prescribed to those individuals.

What is the significance of the automated robotic technology developed by the New York Stem Cell Foundation Laboratory?

The automated robotic technology is significant because it can produce thousands of genetically diverse stem cell lines, which can be used to test drugs and treatments on a wide range of genetic profiles. This technology has the potential to revolutionize drug development by making it more efficient, cost-effective, and personalized.

How does the speaker view the current state of personalized medicine in relation to stem cell research?

The speaker views the current state of personalized medicine as being on the threshold of a new era, thanks to stem cell research. The ability to create genetically diverse stem cell lines and test drugs on them allows for the development of treatments that are tailored to individual genetic profiles, moving away from a one-size-fits-all approach.

Outlines

00:00

🌟 The Promise of Stem Cell Research

The speaker, Joseph Geni, discusses the incredible potential of embryonic stem cells as a form of body repair. These pluripotent cells can transform into any cell type in the body, offering hope for replacing damaged or diseased cells. He emphasizes the transformative impact of stem cell research on disease modeling and drug development, comparing its potential to the eradication of polio. Despite political and financial challenges, the establishment of the New York Stem Cell Foundation Laboratory in 2005 aimed to advance this critical research. The speaker highlights the gap between academic research and pharmaceutical development, and the need for new technologies and research models to bridge this gap. The development of a new technology that generates genetically diverse stem cell lines is presented as a solution to accelerate cures and therapies, allowing for more effective and safer drug development.

05:02

🔍 The Power of Human Stem Cell Models

The speaker continues by describing the groundbreaking discovery of induced pluripotent stem cells (IPS cells), which can be reprogrammed from skin cells. These cells, though not identical to embryonic stem cells, are valuable for disease modeling and drug discovery. An example is given where skin biopsies from patients with ALS were reprogrammed into IPS cells, which were then transformed into motor neurons. This allowed researchers to observe the disease process in a controlled environment, leading to the discovery of previously unknown contributing factors. The speaker argues that without human stem cell models, understanding diseases would be akin to investigating a plane crash without a black box recorder. The potential for using human cells to test drugs is highlighted, emphasizing the current inefficiency and high cost of drug development. The speaker also discusses the need for a more personalized approach to drug development, considering genetic diversity, to avoid one-size-fits-all treatments.

10:03

🛠️ Advancing Stem Cell Technology for Personalized Medicine

The speaker addresses the limitations of current stem cell line production methods, which are manual and time-consuming, leading to inconsistencies. To overcome this, an automated robotic technology has been developed to produce thousands of genetically diverse stem cell lines. This technology is capable of massively parallel processing, which will revolutionize drug discovery by allowing for testing on a wide array of cell types. The speaker envisions a future where drugs are re-screened on these arrays, leading to more personalized and effective treatments. The potential to test drugs on relevant cells, such as brain, heart, and liver cells, is highlighted as a step towards personalized medicine. The speaker concludes by sharing personal connections to diseases like diabetes and heart disease, emphasizing the importance of stem cell research for all.

Keywords

💡Embryonic Stem Cells

Embryonic stem cells are cells from an embryo that have the potential to develop into any type of cell in the body. They are pluripotent, meaning they can morph into all the cells in our bodies. In the video, the speaker highlights their potential for replacing damaged or diseased cells and their role in advancing our understanding of diseases and drug development.

💡Pluripotent

The term 'pluripotent' refers to the ability of a cell to differentiate into any cell type in the body. This is a key characteristic of embryonic stem cells, as mentioned in the script. The speaker emphasizes the importance of pluripotency in the context of stem cell research and its potential applications in medicine.

💡Stem Cell Research

Stem cell research involves the study of stem cells, particularly their potential for use in regenerative medicine and disease modeling. The speaker discusses the transformative impact of stem cell research on disease understanding and drug development, and how it has the potential to change the way we view major diseases like Alzheimer's and diabetes.

💡Induced Pluripotent Stem Cells (iPS Cells)

Induced pluripotent stem cells, or iPS cells, are adult cells that have been reprogrammed to an embryonic stem cell-like state. The script mentions that these cells, although not the same as embryonic stem cells, are valuable for disease modeling and drug discovery. They represent a significant advancement in stem cell technology.

💡Disease Modeling

Disease modeling in the context of stem cells involves using these cells to replicate the conditions of a disease in a controlled environment. The speaker uses the example of turning skin biopsies from ALS patients into motor neurons to study the disease process, illustrating how stem cells can be used to understand disease mechanisms and test potential treatments.

💡Pharmaceutical Companies

Pharmaceutical companies are organizations that develop and produce drugs. In the script, the speaker discusses the gap between academic research and pharmaceutical companies in terms of drug development. The speaker suggests that new technologies and research models are needed to bridge this gap and accelerate the discovery of effective treatments.

💡Genetically Diverse Stem Cell Lines

Genetically diverse stem cell lines refer to a collection of stem cells that represent a wide range of genetic backgrounds. The speaker mentions the development of a technology that can generate thousands of genetically diverse stem cell lines, which is crucial for understanding how different genetic backgrounds might affect disease progression and drug responses.

💡Personalized Medicine

Personalized medicine is an approach to healthcare that tailors treatment to an individual's genetic makeup and health history. The speaker argues that the development of genetically diverse stem cell arrays brings us closer to the era of personalized medicine, where drugs and treatments can be tested for side effects on relevant cells specific to each patient's genetic profile.

💡Drug Discovery

Drug discovery is the process of identifying and developing new drugs. The script discusses how stem cells can be used to test promising compounds on human cells, potentially reducing the time and cost associated with traditional drug development processes. This approach could lead to more effective and safer drugs.

💡One-Size-Fits-All Model

The 'one-size-fits-all' model in the context of drug development refers to the traditional approach where drugs are developed without considering individual genetic differences. The speaker criticizes this model, arguing that it is ineffective and highlights the need for a more personalized approach to drug development that takes into account genetic diversity.

💡New York Stem Cell Foundation Laboratory

The New York Stem Cell Foundation Laboratory is an organization mentioned in the script that was established to advance stem cell research without interference. It represents an effort to create a private safe haven for critical research in stem cell technology, aiming to support and accelerate the development of cures and therapies.

Highlights

Embryonic stem cells are pluripotent and can morph into all cells in our bodies, acting as our body's repair kit.

Stem cells will enable us to replace damaged or diseased cells in the future.

Stem cell research is revolutionizing our understanding of disease and drug development.

Stem cell research could make major diseases like Alzheimer's and diabetes preventable in the future.

The New York Stem Cell Foundation Laboratory was established in 2005 to advance stem cell research without interference.

Large organizations often struggle to innovate in new fields like stem cell research.

A gap exists between academic research and pharmaceutical companies in delivering drugs and treatments.

New technologies and a new research model are needed to accelerate cures and therapies.

A new technology generates genetically diverse stem cell lines to create avatars of ourselves for disease modeling and drug testing.

This technology enables clinical trials in a dish with human cells, making drug development more effective, safer, faster, and cheaper.

Induced pluripotent stem cells (iPS cells) were created by reprogramming skin cells, allowing disease modeling and drug discovery.

Researchers used iPS cells to model ALS and discovered a previously unknown cellular mechanism contributing to the disease.

Stem cells provide an unprecedented window into disease mechanisms, acting as a 'black box' for understanding disease causes.

Current drug development takes 13 years on average, costs $4 billion, and has a 1% success rate.

Drug testing on human stem cells allows for more accurate and faster assessment of drug efficacy and safety.

Genetic diversity must be considered in drug development to avoid 'one-size-fits-all' approaches that may not work for everyone.

The example of Vioxx highlights the dangers of not accounting for genetic differences in drug responses.

Stem cell lines need to be produced in a scalable, automated way to ensure consistency and quality control.

The new technology enables the creation of a genetically diverse array of stem cell lines to advance personalized medicine.

Stem cell research is crucial for developing treatments for common diseases like diabetes, heart disease, and cancer.

Transcripts

Translator: Joseph Geni Reviewer: Morton Bast

So, embryonic stem cells

are really incredible cells.

They are our body's own repair kits,

and they're pluripotent, which means they can morph into

all of the cells in our bodies.

Soon, we actually will be able to use stem cells

to replace cells that are damaged or diseased.

But that's not what I want to talk to you about,

because right now there are some really

extraordinary things that we are doing with stem cells

that are completely changing

the way we look and model disease,

our ability to understand why we get sick,

and even develop drugs.

I truly believe that stem cell research is going to allow

our children to look at Alzheimer's and diabetes

and other major diseases the way we view polio today,

which is as a preventable disease.

So here we have this incredible field, which has

enormous hope for humanity,

but much like IVF over 35 years ago,

until the birth of a healthy baby, Louise,

this field has been under siege politically and financially.

Critical research is being challenged instead of supported,

and we saw that it was really essential to have

private safe haven laboratories where this work

could be advanced without interference.

And so, in 2005,

we started the New York Stem Cell Foundation Laboratory

so that we would have a small organization that could

do this work and support it.

What we saw very quickly is the world of both medical

research, but also developing drugs and treatments,

is dominated by, as you would expect, large organizations,

but in a new field, sometimes large organizations

really have trouble getting out of their own way,

and sometimes they can't ask the right questions,

and there is an enormous gap that's just gotten larger

between academic research on the one hand

and pharmaceutical companies and biotechs

that are responsible for delivering all of our drugs

and many of our treatments, and so we knew that

to really accelerate cures and therapies, we were going

to have to address this with two things:

new technologies and also a new research model.

Because if you don't close that gap, you really are

exactly where we are today.

And that's what I want to focus on.

We've spent the last couple of years pondering this,

making a list of the different things that we had to do,

and so we developed a new technology,

It's software and hardware,

that actually can generate thousands and thousands of

genetically diverse stem cell lines to create

a global array, essentially avatars of ourselves.

And we did this because we think that it's actually going

to allow us to realize the potential, the promise,

of all of the sequencing of the human genome,

but it's going to allow us, in doing that,

to actually do clinical trials in a dish with human cells,

not animal cells, to generate drugs and treatments

that are much more effective, much safer,

much faster, and at a much lower cost.

So let me put that in perspective for you

and give you some context.

This is an extremely new field.

In 1998, human embryonic stem cells

were first identified, and just nine years later,

a group of scientists in Japan were able to take skin cells

and reprogram them with very powerful viruses

to create a kind of pluripotent stem cell

called an induced pluripotent stem cell,

or what we refer to as an IPS cell.

This was really an extraordinary advance, because

although these cells are not human embryonic stem cells,

which still remain the gold standard,

they are terrific to use for modeling disease

and potentially for drug discovery.

So a few months later, in 2008, one of our scientists

built on that research. He took skin biopsies,

this time from people who had a disease,

ALS, or as you call it in the U.K., motor neuron disease.

He turned them into the IPS cells

that I've just told you about, and then he turned those

IPS cells into the motor neurons that actually

were dying in the disease.

So basically what he did was to take a healthy cell

and turn it into a sick cell,

and he recapitulated the disease over and over again

in the dish, and this was extraordinary,

because it was the first time that we had a model

of a disease from a living patient in living human cells.

And as he watched the disease unfold, he was able

to discover that actually the motor neurons were dying

in the disease in a different way than the field

had previously thought. There was another kind of cell

that actually was sending out a toxin

and contributing to the death of these motor neurons,

and you simply couldn't see it

until you had the human model.

So you could really say that

researchers trying to understand the cause of disease

without being able to have human stem cell models

were much like investigators trying to figure out

what had gone terribly wrong in a plane crash

without having a black box, or a flight recorder.

They could hypothesize about what had gone wrong,

but they really had no way of knowing what led

to the terrible events.

And stem cells really have given us the black box

for diseases, and it's an unprecedented window.

It really is extraordinary, because you can recapitulate

many, many diseases in a dish, you can see

what begins to go wrong in the cellular conversation

well before you would ever see

symptoms appear in a patient.

And this opens up the ability,

which hopefully will become something that

is routine in the near term,

of using human cells to test for drugs.

Right now, the way we test for drugs is pretty problematic.

To bring a successful drug to market, it takes, on average,

13 years — that's one drug —

with a sunk cost of 4 billion dollars,

and only one percent of the drugs that start down that road

are actually going to get there.

You can't imagine other businesses

that you would think of going into

that have these kind of numbers.

It's a terrible business model.

But it is really a worse social model because of

what's involved and the cost to all of us.

So the way we develop drugs now

is by testing promising compounds on --

We didn't have disease modeling with human cells,

so we'd been testing them on cells of mice

or other creatures or cells that we engineer,

but they don't have the characteristics of the diseases

that we're actually trying to cure.

You know, we're not mice, and you can't go into

a living person with an illness

and just pull out a few brain cells or cardiac cells

and then start fooling around in a lab to test

for, you know, a promising drug.

But what you can do with human stem cells, now,

is actually create avatars, and you can create the cells,

whether it's the live motor neurons

or the beating cardiac cells or liver cells

or other kinds of cells, and you can test for drugs,

promising compounds, on the actual cells

that you're trying to affect, and this is now,

and it's absolutely extraordinary,

and you're going to know at the beginning,

the very early stages of doing your assay development

and your testing, you're not going to have to wait 13 years

until you've brought a drug to market, only to find out

that actually it doesn't work, or even worse, harms people.

But it isn't really enough just to look at

the cells from a few people or a small group of people,

because we have to step back.

We've got to look at the big picture.

Look around this room. We are all different,

and a disease that I might have,

if I had Alzheimer's disease or Parkinson's disease,

it probably would affect me differently than if

one of you had that disease,

and if we both had Parkinson's disease,

and we took the same medication,

but we had different genetic makeup,

we probably would have a different result,

and it could well be that a drug that worked wonderfully

for me was actually ineffective for you,

and similarly, it could be that a drug that is harmful for you

is safe for me, and, you know, this seems totally obvious,

but unfortunately it is not the way

that the pharmaceutical industry has been developing drugs

because, until now, it hasn't had the tools.

And so we need to move away

from this one-size-fits-all model.

The way we've been developing drugs is essentially

like going into a shoe store,

no one asks you what size you are, or

if you're going dancing or hiking.

They just say, "Well, you have feet, here are your shoes."

It doesn't work with shoes, and our bodies are

many times more complicated than just our feet.

So we really have to change this.

There was a very sad example of this in the last decade.

There's a wonderful drug, and a class of drugs actually,

but the particular drug was Vioxx, and

for people who were suffering from severe arthritis pain,

the drug was an absolute lifesaver,

but unfortunately, for another subset of those people,

they suffered pretty severe heart side effects,

and for a subset of those people, the side effects were

so severe, the cardiac side effects, that they were fatal.

But imagine a different scenario,

where we could have had an array, a genetically diverse array,

of cardiac cells, and we could have actually tested

that drug, Vioxx, in petri dishes, and figured out,

well, okay, people with this genetic type are going to have

cardiac side effects, people with these genetic subgroups

or genetic shoes sizes, about 25,000 of them,

are not going to have any problems.

The people for whom it was a lifesaver

could have still taken their medicine.

The people for whom it was a disaster, or fatal,

would never have been given it, and

you can imagine a very different outcome for the company,

who had to withdraw the drug.

So that is terrific,

and we thought, all right,

as we're trying to solve this problem,

clearly we have to think about genetics,

we have to think about human testing,

but there's a fundamental problem,

because right now, stem cell lines,

as extraordinary as they are,

and lines are just groups of cells,

they are made by hand, one at a time,

and it takes a couple of months.

This is not scalable, and also when you do things by hand,

even in the best laboratories,

you have variations in techniques,

and you need to know, if you're making a drug,

that the Aspirin you're going to take out of the bottle

on Monday is the same as the Aspirin

that's going to come out of the bottle on Wednesday.

So we looked at this, and we thought, okay,

artisanal is wonderful in, you know, your clothing

and your bread and crafts, but

artisanal really isn't going to work in stem cells,

so we have to deal with this.

But even with that, there still was another big hurdle,

and that actually brings us back to

the mapping of the human genome, because

we're all different.

We know from the sequencing of the human genome

that it's shown us all of the A's, C's, G's and T's

that make up our genetic code,

but that code, by itself, our DNA,

is like looking at the ones and zeroes of the computer code

without having a computer that can read it.

It's like having an app without having a smartphone.

We needed to have a way of bringing the biology

to that incredible data,

and the way to do that was to find

a stand-in, a biological stand-in,

that could contain all of the genetic information,

but have it be arrayed in such a way

as it could be read together

and actually create this incredible avatar.

We need to have stem cells from all the genetic sub-types

that represent who we are.

So this is what we've built.

It's an automated robotic technology.

It has the capacity to produce thousands and thousands

of stem cell lines. It's genetically arrayed.

It has massively parallel processing capability,

and it's going to change the way drugs are discovered,

we hope, and I think eventually what's going to happen

is that we're going to want to re-screen drugs,

on arrays like this, that already exist,

all of the drugs that currently exist,

and in the future, you're going to be taking drugs

and treatments that have been tested for side effects

on all of the relevant cells,

on brain cells and heart cells and liver cells.

It really has brought us to the threshold

of personalized medicine.

It's here now, and in our family,

my son has type 1 diabetes,

which is still an incurable disease,

and I lost my parents to heart disease and cancer,

but I think that my story probably sounds familiar to you,

because probably a version of it is your story.

At some point in our lives, all of us,

or people we care about, become patients,

and that's why I think that stem cell research

is incredibly important for all of us.

Thank you. (Applause)

(Applause)