Biology’s New Frontier: The Human Cell Atlas Seeks To Create “Google Maps” for All Cells in the Body

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

[Music]

Mark Masselli: This is Conversations on Healthcare, I am Mark Masselli.

Margaret Flinter: And I am Margaret Flinter.

Mark Masselli: Well Margaret the National Institute of Health has officially kicked off its
much anticipated all of us precis ion medicine initiative it's an ambitious project that’s
seeks to advance medicine by enlisting the participation of a million citizens [inaudible
00:00:21 ] willing to offer up their medical and genomic data to advance the knowledge
and understanding of he alth and disease in a way that has never been possible before.

Margaret Flinter: Well this is program that we’re very proud to be part of at the official
kick off NIH Director. Dr. Francis Collins called the All Of Us Precision Medicine
Initiative one of the most ambitious research projects ever conducted in the United
States and that’s from the guy who oversaw the team that mapped the human genome,
very exciting.

Mark Masselli: It really is, and he is absolutely right it's ambitious, it's ground breaki ng
they’re seeking a million volunteers citizen scientist offer up their genomic biological
medical and behavioral information all to be coalesced in a massive database to allow
researchers to get a more complete understanding of how disease happens and mo re
importantly find ways to prevent it from happening in the first place.

Margaret Flinter: This Precision Medicine Initiative is going to provide so much vital
information on so many aspects of population health across a diverse population of
Americans. As we know health and disease are greatly impacted by people’s racial and
ethnic background, their economic status, their geography, their culture as well as their
genes so this is incredibly exciting to me on the ground floor of this endeavor. I think
we’re all just very excited about where it's going to take us.

Mark Masselli: Speaking of exciting new frontiers in science and human biology that
leads us to our guests today, Margaret, the mapping of the human genome a decade
ago opened up the door to all kinds of new discoveries and there is a similar project just
getting underway that could have huge implications for understanding the fundamental
human biology more completely. Our guest courtiers of the Human Cell Atlas which
seeks to map every cell in the human body.

Margaret Flinter: Dr. Aviv Regev and Dr. Sarah Teichman n will join us to talk about this
massive project currently underway with trillions of cells in the human body. This is
going to take some time but the implications for broadening or understanding of human
biology and health are just astounding and we look forward to hearing more about the
creation of the Human Cell Atlas.

Mark Masselli: Lori Robertson also stops by. She is the Managing Editor of
factcheck.org. You can hear all of our shows by going to CHC Radio or you can also

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

find us on iTunes.

Margaret Flinter: And as always if you have comments please email us at
[email protected] or find us on Facebook or Twitter because we love hearing from
you. We will get to our interv iew with Sarah Teichman n and Aviv Regev of the Human
Cell Atlas project in just a moment.

Mark Masselli: But first here's our producer Marianne O’Hare with this week’s Headline
News.

[Music]

Marianne O’Hare: I am Marianne O’Hare with these Healthcare H eadlines. Walmart
weighing in on the Opioid crisis announcing its cracking down on initial Opioid
prescriptions within the next 60 days saying they will limit prescriptions to just a seven -
day supply. The CDC estimates 115 people die per day from some ki nd of Opioid
overdose. Calorie counts – can we do a food counter near you the law requiring calorie
counts on a number of restaurants food products is now officially in effect. It was part of
the original Affordable Care Act in 2010 but was repeatedly bl ocked by lobbyists in the
food industry claiming it was a hardship. Some evidence suggest posting calorie counts
of foods leads consumers to pause before making unhealthy choices. Kids should not
be consuming any nicotine products that’s the word from FD A Commissioner Scott
Gottlieb on this week’s announced crack down on vaping products being marketed
specifically to kids while teens are smoking fewer combustible cigarettes there has been
an increase in vaping which can lead kids to becoming addicted to n icotine. Gottlieb
says they will be stepping up enforcements of these stricter guidelines. I am Marianne
O'Hare with these healthcare headlines.

[Music]

Mark Masselli: We are speaking today with Dr. Sarah Teichman n , the Head of Cellular
Genetics at the Wellcome Sanger Institute at Cambridge a nonprofit British Genomics
Research Institute and Dr. Aviv Regev, Chair of the Faculty and Co - director of the Cell
Circuits program at the Broad Institute of MIT in Harvard. Both are Co - chairs of the
Human Cell At las Organizing Committee a global collaborative of leading scientists
dedicated to creating the first complete mapping of all human cells. Dr. Regev was
awarded the NIH Director’s Pioneer Award and the Overton Prize having earned a PhD
in Computational Bi ology at the University of Tel Aviv and Dr. Teichma n n has earned
numerous awards as well including the Lister Prize and the Colworth medal. She
earned her bachelors in biochemistry from Trinity College, Cambridge University and
her PhD in Molecular Biology at Cambridge. Sarah and Aviv welcome to conversations
on health care.

Sarah: Thank you.

Mark Masselli: So much, Aviv let's start with you we will be getting to gain an

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

exponential understanding of human biology through the Human Genome Project, that
ultimately led to the sequencing of the human genome often with such dramatic
achievements these discoveries can unleash a whole set of new questions and answers
and you are at the helm of an equally ambitious effort the Human Cell Atlas project and
I’m wo ndering if you could tell our listeners about the goals and the mission of your
endeavor and highlight some of the challenges and opportunities of this undertaking.

Sarah: Absolutely and it's wonderful that you started with the Human Genome Project
becau se just like the Human Genome Project was a project to find the genes which are
one part of the periodic table of elements of the human body the Human Cell Atlas aims
to find all the cells which are another set of elements except that that there are 37.2
t rillion of them. Just that shear number together with the huge size of the human body I
think really underscores how difficult this can be. The other thing that’s difficult is that
the cells are different, different types of cells look different from eac h other. They
express different genes in them and they have different molecules inside them and until
recently we could only really analyze multiple cells at once maybe millions or tens of
millions of them together but the average doesn’t really tell you about the individual cells
and if you don’t know which cells are there you end up with something that can be very
confusing.

Now we have new techniques that allow us to look at individual cells either after we
separate them one from the other or when the cells are in the tissue but looking at all of
their molecules at once. And with these new methods you can think of it as new
microscopes that allow us to look at cells we can really take on this challenge of the
trillions of cells that are different from each other and with this we hope that we can
build the really comprehensive reference map or a periodic table of the elements of the
cells that make up the human body. We can find both the cells that are there in health
but also to use this information in order to better diagnose and monitor and treat human
disease.

Margaret Flinter: I want to ask Sara this question you’ve assembled an international
team of computational scientists and microbiologists and the whole panoply of experts
from so many scienti fic disciplines just decree of framework that can support this kind of
effort. Help our listeners to understand the complexities that are involved in scaling up
the Human Cell Atlas project and how your team is navigating, some of these
foundational logis tics in order to actually bring this project to scale.

Sarah: Sure. The complexities are absolutely right. It is complex. It involves lots of
different disciplines and as you can imagine where that complexity starts is with
acquiring samples of human tissues. That really starts with our friends, the medical
doctors, the surgeons also the biomedical specialists that focus on different tissues and
the biopsies. Those samples are then analyzed using a variety of cutting edge genomic
technologies. Singl e cell genomics is one of them. The excitement there is really the
resolution revolution that’s taken place in genomics where we can now study DNA and
RNA nucleic acids in individual cells. That’s an incredibly exciting. That resolution
evolution is als o going to the spatial level where we can study cells in their spatial

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

context. Then the output from that data generation of course has to be processed. The
technologies are genome biologists I would say technology developers and the data
processing is t hen carried out in a data coordination platform that we’re happy to
elaborate on later and that’s a lot of software developers. People who specialize in
database management of large data flows and organization of humongous data sets.
Then the final sort of level the fourth level is the analysis of that data and the
interpretation and the biological understanding through data mining and that’s where
computational biologists come in machine learning experts biologists who interact with
these computational s pecialists it's a collaborative effort. It's really those four levels that
have really catalyzed the whole Human Cell Atlas consortium. Those are very different
types of people from all over the world that makes it a huge amount of fund, it's a global
ef fort that's very disciplinary.

Mark Masselli: That sounds so exciting I don’t know if there is an IRB and as I
understand you are not only seeking to identify potential billions of cells in the human
body the [inaudible 00:10:00 ] and so on but also to ca tegorize each cell and how it fits in
and how they behave you envision there will be terabytes , maybe zettabytes or maybe
as you said humungous amount of data. Also it's going to be adaptable and accessible
to many scientists and researchers who have been working with NIH and Dr. Collins on
this whole of us initiative and sort of the curating of how scientists access data will be
very important so maybe opine on some of those?

Sarah: So, you were right this is going to be a lot of data I already said 37. 2 trillion cells
in the human body and even if just some of them make it to the Human Cell Atlas that’s
still going to be as a big data as any of the big data endeavors that we’re familiar with.
One of the first activities to get going was our data coordi nation platform which is really
a partnership across multiple institutions including the EBI in the UK UCSC in Santa
Cruz, the Brode Institute where I am. Also engineers from the Chan Zuckerberg
initiative who are buildings together a data coordination pl atform to house all of this data
and make it first of all openly accessible to all you mentioned IRBs everything is with
appropriate consent, but the data will be opened and accessible to all and the data
platform itself is also a open source which means t hat anyone can use the same
platform for many other applications. It's funny that you mentioned all of us in fact some
of the team of engineers that participates in building all of us also participates in building
the data coordination platform. There is also a connection to this more clinical view of
the world. There has been such a explosion of abilities today in the world of software
engineering and machine learning that has happened really in parallel to the explosion
of our ability to collect these kinds of data. As a result we can bring to bear all of this
wonderful engineering and machine learning skill on this kind of problem so that the
data cannot only be housed and processed but to also it can be served with the right
kind of visualization and query tools so that biologists and medical experts can actually
use it.

Margaret Flinter: So, let's talk about governance of the Human Cell Atlas for you there
is four pillars that you’ve identified on which this project is based share with us what
thos e pillars are and some of the standards that the Human Cell Atlas will operate by?

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

Aviv: Sure so in terms of a basic pillar and this is something we share in common with
the Human Genome Project is we want this data to be opened and accessible for the
sc ientific community the medical community and everyone who has an interest in
human cells and tissues and genomic data. Now this is such a big vision and ambition
that we realize that we have to work together internationally to achieve this so
coordination with each other is something that we’re striving towards and we have been
from the very beginning we have an organizing committee and Aviv and co - chair that
there are working groups that are responsible for the data coordination platform the
metadata. Th en really this links also to the way we work and that is that we have the
data coordination platform but also an analysis group where there is a rich eco system
of computational methods and algorithms that are developed by the Human Cell Atlas
working grou p and indeed any [Inaudible 00:13:29 ] group that can then share their
methods across the community. On the biological side, we have collaborative biological
networks that focus on specific systems and organs , so you know there's one for lung,
cardiovascul ar system and brain and these bring together a scientific experts from the
community who want to work together and share their expertise and their progress and
coordinate to map these particular tissues and organs and systems of cells and so on.
And then also we want to catalyze technology development and the Human Cell Atlas, I
think has played a role in this very rapid resolution revolution I would say in genomics,
where a single cell genomics technologies have just become extremely scalable and
robust a nd affordable, so single cells cannot be sequenced but we can actually
measure molecules in the content, their spatial context in the tissue within th eir tissue
context.

Mark Masselli: We're speaking to day with Dr Sarah Teichma n n, Head of Cellular
Genetic s at The Wellcome Sanger Institute at Cambridge, th e nonprofit British Genomic
Research Institute and Dr Aviv R e gev, Chair of the Faculty and Co Director of the Cells
Circuit Program at the Bro ad institute of MIT in Harvard. Co - chairs of the Human Cell
Atl as Organizing Committee, a global collaborative of leading scientists dedicated to
creating the first mapping of all human cells . Aviv, I’m really struck by the fundamental
idea here that we've been looking at cells with 150 - year - old technology. Now we h ave
the dramatic potential for CRISPR technology and I knew that Bro a d Institute has been
front and center in that with the CRISPR 9 and big analytics are accelerating our ability
to collect, interpret data. What could you share with our listeners about th ese recent
technological developments? How they're making this ambitious project possible?

Aviv: You should think about it as though you're trying to build a map, like a google
map. We like to say Google maps for the human body and a map has to have
co ordinates. The coordinates in our case are going to be the expression level of every
individual gene and really the transformational step that has happened is that we can
measure the expression level of every individual genes. For every individual cell i s a
very massive scale. At first, we could do one cell and then a handful of cells and now it
can be tens of thousands, hundreds of thousands and millions are completely within
reach in a single experiment and similarly to that as Sarah described we can d o it for
cells when they are separated from each other and we can do it for the cells when we

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

see not only their coordinates in terms of the expression level of each genome, but we
can see also the real physical coordinates. We can see where they are in t hree
dimensions in a piece of tissue. That's like g etting a new pair of eyeglasses, right?
When you get your glasses and you put them on, all of a sudden everything comes into
[inaudible 00:16:24 ] . That's how cells go t discovered in the first place due to a new
technology , the microscope and that's how we get to rediscover I mean their full
richness using these new approaches, but once we discover that we have the cells, the
immediate next question that we want to ask, what controls them? What makes the m ,
them in their special way and this is where the ability to genetically manipulate cells
become so useful and that's what CRISPR allows us to do, not inside humans, but
outside people, in organoids, in cell culture, in model organisms. You can now start
manipulating the different genes that are highlighted by this reference map and the map
together with algorithms might predict what would happen if I take this gene out, is a
question that becomes very easy to answer with the help of CRISPR. So these two
were really made for each other and in fact, we can take a large number of cells, use
CRISPR to remove one or more gene s from every cell . Then use these single cell
approaches to really measure what was the effect of CRISPR in each cell .

Margaret Flin ter: Very exciting and a complex scientific research requires a lot of
intellect and determination, but it also requires resources and I know the Human Cell
Atlas is getting help from a number of sectors, including the teams at The Bro a d
Institute at MIT in Harvard as well as your research facility, at The Wellcome Sanger
Institute at Cambridge. I also understand there's some significant philanthropic input
from The Chan Zuckerberg initiative, which has a mission of ending preventable
disease by the end o f th is century. Talk with us , how their support is really essential to
supporting this undertaking ?

Aviv: Sure. The Human Cell Atlas relies on the support of many funders, government
funders, many private foundations and large institutional ones, and t hat's what's really
enabled us to hold the community, get together, start the data coordination platform,
start producing the data that will go into the Atlas from the early days. The Wel l come
foundation, also the The Chan Zuckerberg initiative, The Kavli Foundation and now
more recently the NIH HuBMAP for the National Institute of Health and the NIH Cancer
Moonshot . The Chan Zuckerberg initiative ha d provided support very specifically for the
data coordination platform and that's where the data that's cr eated by the HTA projects
will be stored and organized. The y are also supporting pilot projects on technology
development that will all hopefully help the Human Cell Atlas effort.

Mark Masselli: Well, that's wonderful and Aviv you’ve iden tified more tha n a million cell
so far , there's obviously a long way to go and your website suggests that when this
project's completed, it's going to have a dramatic impact giv ing us a better
understanding o n the immune system, the brain, the cancer developmental cells just to
name a few and as you look ahead, what excites you most about the potential of the
Human Cell Atlas to yield new insights and what are the greatest potential for discovery
in biomedical advancement that you think might come out of this?

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

Aviv : You can think of it sort of as an augmented reality of our body, right? That has
impacts for both the most fundamental questions in biology. What are the cell types
that are there and how do they behave in physiology ? And , we're already getting
answers lik e these. We discover new cell types, new cell types in the blood, new cell
types in the lungs , that we didn't even know exist . Then we can ask questions and how
do they behave when things are good . Also h ow things go awry. I think in the context
of dis ease, some of the most basic tests that are done when we’re s ick are basically
single cell assays. The blood draw, you count how many cells are there of maybe six
different types, except that we know that there should be dozens of types, so you can
imagin e a complete blood count 2.0 tells us much more about the status of our body
right now. Same is true when the biops y is taken, and you take a slide, you sta in it
really with those hundred - year - o ld or more techniques to look at tissue sections except
that you will now look at all of the molecules that are there and you will understand how
the cells relate to each other and maybe find new avenues for therapeutic interventions.
When we find genes from genetic studies that are associated with disease, we don' t
know where these genes act, but the Human Cell Atlas, would give us a reference map
to really say this gene is actually important in that kind of cell. That's the next place to
look at , both to understand disease mechanisms and to try and develop the ne w drugs.
When we screen for drugs, we could screen them for giving the cells particular set of
molecules that is desirable and when we treat patients, for example, in wanting to have
much better for toxicity because we would know all of the other cells th at might be
impacted by the same drugs. Both were fundamental biology and for biomedical
research and applications , we think that having a map is much better than having no
map at all , but I think we will leave it at that.

Margaret Flinter: We've been s peaking today was Dr. Sarah Teichma n n, Head of
Cellular Genetics at the Wellcome Sanger Institute at Cambridge and Dr. Avi v Regev,
Chair of the Faculty and Co - Director of the Cells Circuit Program at the Broad Institute
of MIT and Harvard, Co - C hairs of the Human Cell Atlas Organizing Committee. They
are dedicated to creating the first complete mapping of human cells. You can learn
more about their work by going to www.humancellatlas.org or follow their work on twitter
at Human Cell Atlas or the Broad institute at Bro a d Institute and the Wellcome Sanger
Institute at Sanger Instit ute. Sarah , Aviv , thank you so much for sharing your very
exciting and groundbreaking work with us , and for joining us on Conversation s on
Healthcare today.

Dr. Aviv Regev: Thank you so much.

Dr. Sarah Teichma n n: Thank you.

Margaret Flinter: Bye.

[Music]

Mark Masselli: At Conversations on Healthcare, we want our audience to be truly in the
know when it comes to the facts about He althcare reform and policy. Lori Robertson is

Dr Aviv Regev and Dr. Sarah Teichma n n of the Human Cell Atlas

an award - winning journalist and managing editor of FactCheck.org, a nonpartisan,
nonprofit consumer advocate for voters that aim to reduce the level of deception in U.S.
politics. Lori, what have you got for us this week?

Lori Robertson: 20 percent of the children in the United States, it's go to bed hungry.
That's what House Minority Leader Nancy Pelosi said, but we found that she
misrepresented government data. Pelosi claimed that, “ One in five children in America
goes to sleep hungry at night. ” There is no precise measurement for childhood hunger
in the United States, but the census bureau’s most recent Household Food Security
Survey found that about 6.5 million children or 8.8% “lived in households ” in which one
or more child with food insecure. Pelosi's office referred us to a U . S . Department of
Agriculture 2017 report on food security. The USDA administers the Supplemental
Nutrition Assistance Program and several child nutrition programs for low inco me
families in an attempt to combat hunger. The USDAs report is based on the 2016
current population survey, food security supplement , and as Pelosi's office told us the
report says 16.5% of U.S. households with children were food insecure at some point
d uring 2016, but that doesn't mean that the children in tho se households go to bed
hungry. The government differentiate s student security by whether it affect ed adults
only or also children. For children , 8.8% lived in households where at least one child
with food insecure and in 0.8% of households with children, both children and adults
had very low food security. The USDA said that food insecurity with severe enough in
those households that childre n were hungry or skipped meals, and that’s my facts chec k
for this week, I am Lori Robertson, Managing Editor of FactCheck.org.

[Music]

Margaret Flinter: FactCheck.org is committed to factual accuracy from the country’s
major political players and is a project of the Annenberg Public Policy Center at the
Uni versity of Pennsylvania. If you’ve a fact that you would like checked, e - mail us at
www.chcradio.com , we’ll have FactCheck.org’s, Lori Robertson, check it out for you,
here on Conversations on Healthcare.

[Music]

Margaret Flinter: This is Conversations on Healthcare, I am Margaret Flinter.

Mark Masselli: And I am Mark Masselli, peace and health.

[Music]

Conversations on Healthcare broadcast from the campus of WESU at Wesleyan
University, streaming live at www.wesufm.org and brought to you by the Community
Health Center.