Article published by Baillie Gifford in November
2021.
Written by Rose Nguyen and Julia Angeles.
Disclaimer at the end of the article.
Businesses Exploiting the beginnings of the Digital
Human Concept
Businesses : - Verve, Denali and Grail
What do Grail, Verve and Denali have in common? The
ability to turn biology into information science and put it to revolutionary
use transforming our health and wellbeing.
Throughout modern human history, there have been
periods of great technological innovations that have radically disrupted and
changed the ways in which societies and economies work. From the steam engine
to electricity to computing, these incredible inventions which were the
hallmarks of the previous industrial revolutions have completely transformed
our lives over the past two centuries. We believe that another revolution is
underway – this time in relation to biology. If the previous industrial revolutions
were about inventing new things to make our lives better, then the biological
revolution is about pushing our understanding of biology and unpacking millions
of years of evolution, the insights from which will transform healthcare and
redefine our health and wellbeing.
The facts of life
For millennia, much of biology has remained a black
box. The complexity, sophistication, and intricacy of the human body has
prevented us from making significant inroads into reducing the number of deaths
from cancers, heart diseases, Alzheimer’s and so on. Cardiovascular disease
remains the number one killer globally, claiming approximately 18 million lives
per year. One in two people in the UK will develop cancer over their lifetime.
And if we are lucky enough to live beyond 80 years, one in six of us in the UK
will develop dementia.
These are grim statistics, but our hope is that the
figures will dramatically reduce as the biological revolution unfolds, and we
will return to specific examples of companies radically improving the outcomes
in these areas later in the paper. Before exploring where a biological
revolution could lead, it is helpful first to understand where it has come
from.
The study of life
The biological revolution has been in the making
for a long time. Biology in Greek means “the study of life”, and this subject
has always been at the centre of human interests. However, there have been many
false premises and setbacks along the way.
An example is Pythagoras’ theory of ‘spermism’. His
hypothesis was that babies were created purely from male sperms, which
circulated around the male body to gather instructions about making different
body parts. From there the sperms were nurtured and matured in the woman’s
womb. The problem with this theory, as Aristotle identified two centuries
later, was that the sperms couldn’t possibly produce female babies simply
because men don’t have female parts. Looking back, such theories might sound
absurd, but it is hard to blame the thinkers when they lacked the proper tools
and technologies we now have to study life.
Things began to change with the invention of the
microscope. For the first time, we were able to see the components of life and
other microorganisms which we didn’t know existed. This led to a burst of new
knowledge, the ‘Cambrian explosion’ moment of biology. As the technologies have improved over time,
it is now possible to observe the cellular machinery, how different proteins
interact with each other, leading to a much better understanding of biology and
how to manipulate it.
The code of life
One of the most important technologies in life
sciences, the one that propelled our knowledge of biology to a new height, is
gene sequencing. Gene sequencing allows us to read the code of life. It’s
fascinating that despite the complexity of biology, the code of life is written
with just 4 DNA letters – A, T, C and G. Hidden behind what seems to be the
chaos and unpredictable emergent properties of biology is in fact a rather
orderly information system. There is great potential to turn the anarchy of
biology into an information science. By using experimental observations,
machine learning, gene editing and other advanced techniques, we can start
mapping out the genetic circuits within a cell and understand how different
genes relate to each other at the tissue level, organ level, and eventually for
the whole organism.
Over the past 20 years, the cost of sequencing a
whole human genome has declined dramatically from over $100m to under $1000
today. If Illumina has led the charge in bringing down the costs of sequencing,
then younger companies, such as 10X Genomics, have been striving to increase
the resolution of sequencing. Now we can sequence at the individual cell level,
and compare the genomes of healthy cells versus diseased cells to figure out
what genes are responsible for the disease. Using single cell sequencing, we
can also start to build a map of cell-to-cell interaction. Imagine for a
moment, if we were to master human biology and learn to configure it like we
would a computer. If a part goes awry, we know exactly what’s wrong and how to
fix it. Developing a drug to treat a disease could be as simple as writing a
new software to fix a computer virus.
The
bright side of life
Whereas
we normally associate revolutions with a big and transformative change,
sometimes they are generated by the accumulation of gradual changes,
imperceptible at the time. We believe that the life science industry is
building momentum for a transformational change in the same spirit, with the
biological revolution having been quietly gathering pace over the past decades.
During
2020, we witnessed this radical shift first-hand. The reason we could develop
the vaccine against Covid-19 so rapidly was due to the accumulation of lots of
tiny changes that have taken place across many different industries over the
past few decades. These include material science, chemistry, biology, genomics
and data science. On its own, each improvement would have been insufficient to
move the dial, but in combination, it allowed companies to create effective
vaccines at an unprecedented speed. Let’s explore a few other examples where we
see the potential for transformational change in healthcare.
Specific Examples by Business
Cardiovascular (Verve Therapeutics)
Cardiovascular diseases are diseases of the heart and blood
vessels, with lifestyle being a major risk factor. What if we could mitigate
the risks of suffering from heart diseases regardless of lifestyle? Or better
still prevent heart diseases altogether?
Verve Therapeutics hopes to find out. It is developing a
single-course gene-editing medicine to lower the risk of cardiovascular
diseases. The company’s technology is based on advances in several areas.
First, large population genomic studies have revealed new
insight that there are certain genetic variants that confer natural protection
against cardiovascular diseases for some people. By manipulating the genes
we’ve discovered that can lower or raise cholesterol, it is possible to provide
a natural protection for those who are less fortunate.
Second, ground-breaking gene editing tools, so-called base
editing technology, enable us to manipulate genes precisely and efficiently.
And finally, biotech companies have made a lot of progress
on how we deliver gene editing tools and other medicines to cells. Packaged
within a lipid nanoparticle, mRNA (as used in some Covid-19 vaccines) codes the
production of a gene editing tool: human cells have literally become the
manufacturers of the gene-editing tool that then goes and modifies the targeted
cells within their own body.
In isolation, each of these advances might not solve the
enormous problem of cardiovascular diseases. However, when combined, they offer
a step change in the way we can prevent and treat these diseases.
Alzheimer’s (Denali Therapeutics)
Advances in many different sciences have enabled Denali
Therapeutics to develop new approaches to the treatment of neurodegenerative
diseases. One of the longstanding challenges in addressing neurodegenerative
diseases has been our inability to find a way to deliver large molecular drugs
through the blood brain barrier (BBB). While the BBB helpfully stops harmful
substances getting into the brain, it also unhelpfully prevents many drugs
getting into the brain and therefore limits our abilities to treat and prevent
Alzheimer’s and other conditions.
Denali is making great progress in addressing this
challenge and the company has already demonstrated its ability to get complex
molecules into the brain. In addition to unlocking access to the brain, Denali
is also leveraging on advances in genetics, pathology and cell biology to
identify pathways that trigger neurodegeneration. This brings us closer to
establishing what the underlying causes of diseases are and therefore
increasing the chances of developing effective drugs.
Cancer (Illumina/Grail)
Unfortunately, despite many decades of cancer research, the
disease remains the second largest killer in the world. If we were able to
diagnose cancer at an early stage, it could substantially improve the outcomes
for patients and provide an opportunity to turn cancer into a chronic disease,
rather than a killer.
Grail is one of the leaders in the early diagnosis of
cancer. The company provides a test, based on a single blood draw, that can
diagnose dozens of cancers in their early stages. This test can be performed in
the doctor’s office, possibly annually as part of the general health check-up
for seniors.
Grail’s achievement so far is already nothing short of
transformational. What many have failed to appreciate is how powerful different
technologies can be when they are brought together, leading to even more
radical change than the sum of parts. In Grail’s case it has combined
breakthroughs in genome sequencing and AI to great effect.
A new phase of life
While we have only highlighted a few disease areas, it is
important to note that the biological revolution is impacting the entire
spectrum of health. As investors in transformational health companies, we are
excited about identifying and supporting innovative companies through the
biological revolution.
Risk Factors and Important Information
The views expressed in this communication are those of Rose Nguyen and Julia Angeles and should not be
considered as advice or a recommendation to buy, sell or hold a particular
investment. They reflect personal opinion and should not be taken as statements
of fact nor should any reliance be placed on them when making investment
decisions.
This communication was produced and approved in November
2021 and has not been updated subsequently. It represents views held at the
time of writing and may not reflect current thinking.
