How to make your organs last longer | Quin Wills | TEDxNoVA

Summary

In this insightful talk, the speaker introduces 'Betty,' a revolutionary machine that can sustain a human liver outside the body for up to five days, allowing for advanced liver assessments before transplants. The presentation delves into cutting-edge RNA medicines designed to reprogram donor organs, potentially transforming the future of organ transplantation. It also touches on the challenges of developing therapies for chronic liver disease, advocating for a new approach that leverages AI and human collaboration to expedite the discovery and testing of life-saving treatments.

Takeaways

• 🔬 Betty is a machine that can keep a human liver alive outside the body for up to a day, used in clinics to assess liver health before transplants.
• 🏥 The Liver Intensive Care Unit (IU) in Manhattan is a unique facility where scientists, technologists, and clinicians work on extending the life of livers to five days using advanced technology.
• 💊 The project involves injecting livers with RNA medicine, a sophisticated method that can alter gene behavior and target specific liver cells, representing a new approach to liver medicine.
• 👨‍⚕️ The speaker has early-stage liver disease, highlighting the personal connection to the work and the urgency of finding solutions for liver health.
• 📈 Shocking statistics: one in three people may have liver issues, and one in six of us could live to be a hundred, facing chronic diseases of aging like liver failure.
• 🌐 The aging population is increasing, with one in four people expected to be over 60 in 30 years, raising concerns about the longevity and health of our organs.
• 🔬 The process of creating new medicines involves three steps: generating hypotheses, testing them, and conducting clinical trials, each with its own challenges.
• 🤖 AI and deep learning are used to analyze liver biopsies, creating detailed atlases from genes to cells to tissues, helping understand liver function and dysfunction.
• 🧪 Labs in Oxford and Taipei are working on human liver models, using both bottom-up and top-down approaches to study liver function and develop therapies.
• 💉 The goal is to develop therapies that can repair livers, potentially eliminating the need for transplants by using medicines that target specific liver cells.
• 💻 Computational models and AI avatars are being developed to predict liver responses, accelerating the process of developing new therapies and reducing costs.

Q & A

What is the primary function of the machine called Betty?

Betty is a machine designed to keep a human liver alive outside the body for up to a day. It is used in clinical settings to assess the health of livers before they are transplanted into another human being.

What is the purpose of the Liver Intensive Care Unit (LICU) in downtown Manhattan?

The LICU in downtown Manhattan is where a team of scientists, technologists, and clinicians are working to modify the use of liver machines to keep livers alive for not just one day, but up to five days. The goal is to treat organs as patients and improve their viability for transplantation.

What is the significance of the RNA medicine used in the liver machines?

The RNA medicine is a sophisticated form of treatment that is programmed to change the behavior of specific genes and target only very specific cells in the liver. This represents a new way of thinking about liver medicines, potentially reprogramming donor organs that are too old or diseased to be suitable for transplantation.

Why is there a focus on the liver in this context?

The focus on the liver is due to the speaker's personal experience with early stages of liver disease. Additionally, liver disease is a common condition that can lead to the need for a liver transplant, which is a critical and often life-saving procedure.

What is the 'scary statistic' mentioned in the script about liver transplants?

The 'scary statistic' is that if you end up on a liver transplant waiting list, there is a good chance you will die before a healthy enough liver is found for you.

What is the speaker's perspective on the aging population and its implications?

The speaker views the aging population as a potential 'aging epidemic' that could be as significant as global warming. The challenge is to create a society where people can live healthy lives into their 100s, which involves rethinking healthcare and treatment for chronic diseases of aging.

What are the three steps in developing a therapy to reduce scarring in human livers as described in the script?

The three steps are: 1) Idea phase (hypothesis generation) where potential genes affecting scarring are identified. 2) Testing the hypothesis and making a medicine, which often involves animal testing and can take many years. 3) Clinical trials in humans, which are lengthy, expensive, and often fail.

How does the speaker propose to address the challenges in developing transformative medicines for chronic diseases of aging?

The speaker suggests addressing the challenges by learning more about human biology, reducing reliance on animal models, and improving clinical trials to be less time-consuming, less expensive, and less risky.

What role does AI play in the process of studying and treating liver diseases as described in the script?

AI plays a crucial role in analyzing large and complex datasets from liver biopsies. It uses self-supervised deep neural networks to learn without human supervision, reducing complex data into simpler core elements that can be understood and collaborated on by humans. This helps in building detailed atlases from genes to cells to tissues to organs and whole patients.

What is the ultimate goal of the speaker's research and the use of AI in medicine?

The ultimate goal is to create a society of healthy 100-year-olds where people can live longer, healthier lives. The speaker hopes that their research and the use of AI will help in developing therapies that can repair organs like the liver, potentially eliminating the need for transplants.

Outlines

00:00

🔬 Advanced Liver Preservation Technology

The script introduces a cutting-edge medical device named Betty, capable of keeping a human liver alive outside the body for an extended period, initially for one day but being developed to last up to five days. This technology is utilized in a unique Intensive Care Unit (ICU) for organs, specifically livers, where scientists, technologists, and clinicians work on enhancing liver preservation. The purpose is to assess liver health before transplantation. The narrative also delves into the innovative use of RNA medicine, which is programmed to target specific cells within the liver, marking a new approach to liver treatment. The speaker shares a personal connection to liver disease and emphasizes the importance of liver health, citing statistics about liver disease prevalence and the challenges of liver transplant waiting lists.

05:00

🧬 Rethinking Medicine Development for Liver Scarring

The speaker discusses the traditional process of developing therapies for liver scarring, which involves hypothesis generation, testing on animals, and eventually clinical trials in humans. This process is time-consuming, expensive, and often results in failure. The speaker criticizes the reliance on animal models for predicting human responses and the inefficiency of lengthy clinical trials. To address these issues, the speaker's team is employing a new approach that includes the use of AI algorithms to analyze large datasets from liver biopsies, aiming to understand liver function and dysfunction at a detailed level. This method is compared to the work of artists who simplify complex scenes into core elements, illustrating a similar approach to simplifying complex biological data.

10:02

🛠️ Human Models and AI for Liver Therapy Development

The script explains the team's innovative methods for creating human liver models to test hypotheses and develop therapies. They use a combination of bottom-up and top-down approaches, involving detailed analysis of liver biopsies and the creation of miniature liver models. These models are then used to test potential therapies, with the goal of repairing liver function outside the body and potentially eliminating the need for transplants. The process is accelerated by using AI to analyze data and make predictions, which helps to quickly identify promising therapeutic targets. The speaker highlights the success of this approach in significantly reducing the time and cost associated with traditional drug development methods.

15:04

🌐 Vision for Global Organ ICUs and Transformative Medicine

The speaker concludes with a vision of a future where organ ICUs are commonplace, not just for livers but for other organs like kidneys, hearts, and lungs. This vision includes the rapid development and testing of therapies without the long wait times associated with current methods. The hope is that these advances will allow for the transformation of millions of lives by improving organ health and potentially eliminating the need for organ transplants. The speaker emphasizes the importance of this work in the face of an aging population and the increasing prevalence of chronic diseases.

Keywords

💡Liver Intensive Care Unit (IU)

The Liver Intensive Care Unit (IU) is a specialized facility designed to keep human livers alive outside the body for an extended period, typically for a day. In the context of the video, this technology is revolutionary as it allows surgeons to assess the health of livers before transplanting them into patients. The script mentions the IU as a place where cutting-edge technology is being used to potentially extend the life of livers to five days, emphasizing the importance of organ preservation in the field of transplant medicine.

💡RNA Medicine

RNA Medicine refers to therapeutics based on RNA molecules, which are different from traditional drugs. In the video, it is described as a sophisticated form of medicine that can be programmed to alter the behavior of specific genes and target particular cells within the liver. This is a novel approach to treating liver diseases by reprogramming donor organs that may be too old or diseased for direct transplant, showcasing a new frontier in personalized and targeted medicine.

💡Chronic Diseases of Aging

Chronic Diseases of Aging are health conditions that result from the long-term wear and tear on the body, leading to the gradual deterioration of organ function. The video discusses how these diseases, such as liver failure, heart disease, and joint degradation, are becoming more prevalent as life expectancy increases. The script emphasizes the need for new approaches to medicine that can address these chronic conditions, which are expected to be a major health challenge in the context of an aging population.

💡Aging Epidemic

The term 'Aging Epidemic' in the video refers to the growing concern of an increasing number of elderly individuals in the population and the associated health challenges due to chronic diseases of aging. The script suggests that this demographic shift could be as significant as global warming, highlighting the urgency and scale of the issue. It implies the need for societal and medical innovation to ensure healthy aging and quality of life for the elderly.

💡Self-Supervised Deep Neural Network

A Self-Supervised Deep Neural Network is an artificial intelligence algorithm that can learn from data without human supervision. In the video, such a network is used to analyze images of liver biopsies, breaking them down into smaller images and identifying patterns that can represent complex liver data. This technology is crucial for understanding liver function and dysfunction at a detailed level, which is essential for developing new therapies.

💡Hypothesis Generation

Hypothesis Generation is the initial phase of scientific research where ideas are formed about potential relationships or effects. In the context of the video, it involves identifying genes that may affect liver scarring and could be targets for therapy. The script describes this process as a critical first step in developing new medicines, where traditional methods like reading papers and using databases are being supplemented with more innovative approaches.

💡Clinical Trials

Clinical Trials are research studies that involve human participants to determine the safety and effectiveness of new medical interventions. The video discusses the challenges of conducting clinical trials for chronic diseases of aging, such as the long duration, high cost, and high risk of failure. The script emphasizes the need for more efficient methods to test new therapies, reducing the time and resources required to bring new treatments to patients.

💡Human Data

Human Data in the video refers to information collected from studying actual human organs, such as livers, in a lab setting. The script mentions that the new approaches being developed can generate human data on new therapies in days rather than years, which is a significant acceleration in the drug development process. This rapid data generation is crucial for quickly identifying effective treatments and moving them towards clinical trials.

💡AI Avatar Human Liver Models

AI Avatar Human Liver Models are computational representations of human livers that use artificial intelligence to make predictions about the effects of potential therapies. The video describes these models as a tool to increase the success rate of identifying effective genes for treatment. By simulating liver responses to therapies, these models can help scientists make quicker and more accurate decisions about which treatments to pursue, reducing the time and cost of drug development.

💡Organ ICU

The concept of an Organ ICU in the video refers to a future vision where intensive care units are not only for patients but also for organs, such as livers, kidneys, hearts, and lungs. These units would allow for the advanced treatment and preservation of organs, potentially reducing the need for transplants by repairing organs outside the body. The script suggests that this could revolutionize transplant medicine and extend the life of many organs.

Highlights

Introduction of Betty, a machine that can keep a human liver alive outside the body for a day.

Betty is used in the clinic to assess liver health before transplant.

The liver Intensive Care Unit (ICU) is a unique setting where the 'patient' is an organ.

Use of RNA medicine to modify the behavior of specific genes in the liver.

Aim to reprogram donor organs that are too old or diseased for transplantation.

Personal story of the speaker's early stages of liver disease and its unnoticed symptoms.

One in three people may have a liver similar to the speaker's, highlighting the prevalence of liver disease.

The grim reality of liver transplant waiting lists and the high mortality rate.

Projections of increased life expectancy and the implications for organ health and chronic diseases.

The concept of an 'aging epidemic' and its potential parallels to global warming.

The use of sibling mice from a lab to demonstrate the effects of a treatment that removes age-accumulated cells.

The need to rethink medicine as not just curing disease but maximizing health span.

The challenges in creating transformative medicines for chronic diseases of aging.

The three-step process of creating a therapy: idea generation, hypothesis testing, and clinical trials.

The limitations of traditional methods like animal models and the high failure rate of clinical trials.

The innovative approach of using AI and deep neural networks to understand liver function.

Building detailed atlases from genes to cells to tissues to organs for a comprehensive understanding.

The development of human liver models to test hypotheses and therapies more efficiently.

The potential of these models to reduce the time from idea to human data on a new therapy from years to days.

The role of computational models and AI in predicting successful therapies and accelerating the development process.

The vision of organ ICUs worldwide for advanced organ preservation and therapy testing.

The speaker's hope for the transformative impact of this science on millions of lives.

Transcripts

[Music]

so let's speak about the elephant in the

room this is Betty everyone say hello to

Betty Betty oh they respond this is this

is fantastic uh this is a machine that

can keep a human liver alive outside of

the Body for a day it's really cutting

edge technology the surgeons are already

using in the clinic to assess how well

livers are doing before transplanting

into another human being this is our

liver Intensive Care Unit or IU in

downtown Manhattan here are a very

talented team of scientists

technologists and clinicians are

modifying how we use those five liver

machines to keep livers alive not just

for one day but five days this is a very

different kind of ICU where the patient

is an

organ so why are we doing this

each one of our livers gets injected

with a vial of white powder like this

this is an RNA medicine not exactly like

the co RNA vaccines you'll be familiar

with this is more

sophisticated this medicine is

programmed not only to change the

behavior of any Gene that we want it's

also programmed to only go to very

specific cells in the liver you're

looking at what is in effect a new way

of thinking about liver medicines Where

We Are reprogramming donor organs that

are too old too disease to go to the

patients who really need them why are we

doing the liver

though this is a picture of my

liver not pretty is

it a healthy liver doesn't look quite so

pale or so plump and that's because I

have early stages of liver disease now

you can't tell by looking at me and I

feel absolutely fine and I will keep

feeling absolutely fine I promise for

many many years until at some stage my

liver May scar so badly that it will

fail and when it fails my only option

will be a liver

transplant are you ready for a very

scary

statistic I'm going to ask everybody in

this room to look to the person on your

left are they're so interact oh they

love the audience participation here and

then to your

right no your other

left

one in three of you has a liver that

looks like mine and the sad reality is

that if you end up on a liver transplant

waiting list there is a good chance that

you will die before a healthy enough

liver is found for

you ready for another

statistic one in six of us in many parts

of the world born now can expect to live

to be a hundred what will these healthy

100y olds mostly be dying of cancer

infections no the wear and tear of old

age and disease exactly what's happening

with my

liver Hearts kidneys failing after years

of high blood pressure bones crumbling

joints degrading breathing becoming

difficult after a lifetime of pollution

we call these chronic diseases of Aging

in fact many times we really just mean

it's your parts wearing

out and this isn't a problem we've

always had to face right as a species in

the Middle Ages lucky was reaching in

your mid-30s now lucky is almost three

times that in 30 years time one in four

of us are going to be over the age of 60

and I guarantee you will be expecting

your parts to be living much longer than

they ever

have we are beginning to approach what

some of us refer to as an aging epidemic

and many of us believe could be as

important as global

warming so what do we do how do we

create a society of healthy 100 Ys where

your 60s are about that second career

that you've always wanted and not

retiring what's that real change that we

need you're looking at sibling Mice from

a lab and Mayo Clinic

they are the same age the one on the

left is showing its real age whereas the

one on the right still looks young and

healthy this young one has been given a

treatment that removes unwanted cells

that tend to accumulate with age think

of it as cleaning the rust out of its

mousy

Parts incredible results like this are

really forcing us to I think rethink

what medicines mean to us not just

agents for curing disease but agents for

maximizing Health span this is the real

change that many are advocating for but

I don't believe this is

enough while I do believe it's very

important that we think hard about the

kind of medicines we'd like to make I

believe it's equally important that we

rethink how we make medicines and it's

that belief that brings me here on a

stage standing next to

Betty let me

explain let's say

you want to make a therapy you want to

make a medicine that reduces scarring in

human livers roughly speaking there are

three steps step one this is the ideas

phase this is where we call this

hypothesis generation where you come up

with those that list of genes that you

think could affect scarring and which

could be targets for your

therapy how do we do this well

traditionally one one method has just

been reading a lot of papers looking at

what university scientists play with we

call this the Street Lamp approach

because it's a little like searching for

your lost Keys only near Street lamps

because that's where the light

is thankfully a lot of scientists have

now come together to build incredible

databases like the UK bio bank that has

the genetic and disease information for

half a million

people these databases are definitely

helping illuminate a lot more but the

sad reality is they don't help us

understand a lot about the fun

fundamentals of what our internal organs

are

doing there is so much about liver

function and dysfunction that we just

don't understand and without this

knowledge it becomes very difficult to

make a medicine bringing us to step two

which is test your hypothesis and make a

medicine simple no this stage lasts many

many years I ofer a decade or more

here's the rub we of course can't

experiment in human beings so we do a

lot of work in animals we poison mice we

actually perform very cruel surgeries on

them to make the live a scar all the

while knowing that this is very poorly

predictive of what we can expect in

human beings mice only live for about

two years whereas the scarring we're

talking about can build up over decades

if I'm to be very honest with you about

the mice that I showed you we have no

idea if we'll achieve the same result in

longer lived humans the reality is we

have cured so so many diseases in our

road and friends only to find out that

these therapies are effectively useless

by the time we reach step three which is

Testo therapy in a human

being here's the problem with clinical

trials for chronic diseases of

Aging they take very long are very

expensive and usually

fail you can spend easily $100 million

doing this kind of scarring trial

only to find out the mice got it very

wrong isn't that crazy no wonder it is

so difficult to make the kind of

transformative medicines that we need so

that you can look forward to your

60s so what do we do then well we solve

this by taking on the challenges in

those three steps we don't know enough

human biology we're overly reliant on

animal models and clinical trials that

are too long too expensive and too high

risk

this is the challenge the team and I set

ourselves when we decided to make

medicines in a very different way and

I'd like to walk you through just the

first Two

Steps step one learn about how the liver

actually works at

scale to do this we've set up labs in

Europe Asia and the us where we are

sequencing and studying livers in

incredible

detail here's one example of how we do

things you're look looking at an image

of a biopsy this is a biopsy from a

single liver one of a thousand livers

that we studied in the

UK we take that image and we break it up

into the smaller images you see there we

then feed those images into an AI

algorithm that we call a self-supervised

deep neural network this algorithm can

learn without human

supervision and when it does that it's

able to paint an image like this

this image this abstraction is how the

algorithm is actually making sense of

very big very complex data across very

many livers is taking all of that and

reducing it down to what it sees as

simpler core

elements this is very similar to how

artists such as mandrian looked at the

world around them and reduced it to

simpler core

elements this is mandan's depiction of

New York City

which has famously been hanging upside

down all of these years it's pretty

obvious which way up is

no our algorithm does exactly this it

takes very big ideas and reduces it down

to something that simpler human Minds

can collaborate with and we're doing

just that so for example that element

over there is something that we

recognize as fat buildup inside the

liver which I'm showing you here is the

light Parts in this biopsy

we can also map these elements to every

Gene and here I'm showing you the very

beautiful spatial expression of one gene

in green we then can map all of these to

Patient traits and we've done that for

blood patient histories uh and even

General features like body weight in

doing this we're building up very

detailed atlases from genes to cells to

tissue to organs and then whole patients

but that's not enough we want to be able

to test our hypotheses step two in human

models our lab and Ox takes a bottom up

approach and by that I mean we take lots

of different types of cells from

different donor livers and we bring them

back together to build little models of

what we see as liver function and

dysfunction our lab in taipe takes a

more top- down approach this is the only

lab in the world that has set up a

clinical Network to receive biopsies

from disease livers turning each biopsy

into about 50 slices and then culturing

culturing these slices in the lab as

many diseased

microl using these approaches we're

learning a lot about human biology and

making therapies to change the biologies

that we see bringing us to the final

stage that is testing our Therapies in

whole human livers here we look at how

we can improve the function in the

livers so in effect during the clinical

trial before the clinic

trial here's a really cool thing so yes

we are repairing livers outside of the

body but remember I said to you that

these medicines are programmed to go to

certain cells in the liver that's

because once we've learned how to do

that these medicines become a shot in

the arm of patients with liver disease

going directly to their livers to repair

their livers inside their body hopefully

one day doing away with the need for

transplant all

together here's another really cool

thing so remember I said that step two

from ideas to step three clinical trials

that part often takes 10 years or more

using these kind of approaches we're

able to go from Step One to a new

therapy to generating human data on a

new therapy in days not yours so sure I

mean I will agree these aren't perfect

models no model ever is but what this is

helping us to do is learn to fail fast

so that we can be a lot more sure about

the therapies we want to take forward to

step

three I want to share one more thing

that I think is super cool so we're not

just generating a lot of data genes and

cells and livers we're actually building

computational models our goal here is

that AI Avatar human liver models make

such good predictions that they start

helping our scientists come to the right

conclusion even quicker and we're doing

just that so this is actual data from

our

lab here I'm showing you the low success

rate you can expect using traditional

experimental approaches so if we take

randomly take genes we take 100 genes

250 genes and then 500 genes at most we

can expect to capture about just over 3%

of the really interesting genes out

there if we take these experimental

results the data and feed it back to an

algorithm the algorithm can have a look

at what's worked and what hasn't and

then make suggestions about which genes

we really want to be looking at when we

do that and go back to the lab our

success immediately jumps

up so in a single step from humans

talking to algorithms talking back to

humans we've already dramatically

increased our success and crucially at a

fraction of the price it would have cost

us if we just used traditional

experimental approaches what I really

like about this kind of story is that in

an age where frankly I feel there's a

lot of hype around AI what it will do

and how it might Supply to all of us

we're coming to a more pragmatic

conclusion that algorithms and humans

actually make for really great

collaborators and it's this lesson that

I believe has very deep implications

Beyond just chronic liver disease to

other diseases so for example machines

exist s that not only keep your liver

alive but kidneys heart

lungs imagine when one day this is not a

liver ICU but an organ

ICU imagine these organ icus all over

the world where donor organs that AR

transplanted can

go imagine scientists being able to

really form ideas and quickly test out

therapies without having to wait for

years the current hope in transplant

medicine is that each one of your organs

may get to save

aif my hope with this kind of science is

that the gift of my organs will get to

transform millions of lives thank

you