Luke Timmerman: “Hood: Trailblazer of the Genomics Age” | Talks at Google

[MUSIC PLAYING] KRISHNA YESHWANT: Thank
you so much for joining us, Luke as we were
getting introduced, we’ll definitely talk a
bunch about Lee Hood based on the work that you guys– that you put together. But I really wanted to
start by talking about you. And I was just asking you a
moment ago, how often it is– I’ve seen any number of times
you’ve moderated an interview, or moderated group of
panelists, but how often are you on this end of the interview? LUKE TIMMERMAN:
Well increasingly I am on the receiving
end of these. I’m speaking on Public Radio
from time to time, at panels, sometimes people want to know
at industry events, what’s hot an interesting
for the journalists. So– KRISHNA YESHWANT: Interesting. LUKE TIMMERMAN: Now and then. KRISHNA YESHWANT: Perfect. Well great. I have a whole bunch of
awkward questions here for you. So let’s get started
with a couple good ones. Maybe just so folks know a
little bit more about you, can you tell us a little
bit about your background? How you made the path from– I think you grew up in
Wisconsin if I remember, all the way to being
a biotech journalist, and doing amazing
work you’re doing now? LUKE TIMMERMAN: Yeah, sure. So I studied journalism at
the University of Wisconsin. Wasn’t sure what I
would specialize in or even if I would specialize. That wasn’t really a thing of
the 90s when I was coming up. But I ended up getting a
job at the Seattle Times as a general business reporter. And about a year
into that stint, I had shown some
ability to explain jargony, boring kind of
subjects to the editors in plain English. I could bring those
things to life. And at the time,
the newspaper still had a biotechnology beat
and a dedicated reporter on the business staff. And I– there were two openings. It’s interesting, at
the time I was about ready to get promoted,
and one was for biotech, and one was for retail. So I could have
covered Starbucks and Costco and Amazon,
and my whole path would have been different. But I looked at biotech and
I thought, there’s science, there’s human health,
there’s business, there are ethical
issues, there are all these interesting
characters, like charismatic entrepreneurs,
it all changes really fast, there’s no one dominant company. So in Seattle at the
time, on business desk, if you wanted to
get ahead, you would cover Boeing or Microsoft. One of the big companies. But I kind of looked at
some of the stories that were coming out of
there and thought, oh gee, another jet
order for Singapore, or the latest
version of Windows. I thought biotech had rich
ingredients for storytelling. And so I kind of dived in. That would have been 2001. It was just in the wake of
the Human Genome Project. And I thought, this is
getting interesting. I can imagine doing this a long
time and not getting bored. KRISHNA YESHWANT: We’ll come
back to Seattle in a moment, because I’d love to hear kind of
what you’ve seen in the Seattle and Northwest geography,
because there’s obviously been a lot of change there. But you then ended
up at Xconomy, and then more recently you’ve
started the Timmerman Report. You’ve done the book. You’ve done– there’s a
podcast that you’ve started. You had a brief bit
where you’re doing some stuff with STAT News. So just can you give us a
sense of how you ended up at Xconomy and then really kind
of your own entrepreneurial journey from going from a
larger publication to going off and doing your own thing? How did you decide to do that? LUKE TIMMERMAN: Yeah, well,
this being Google I mean, you understand the
disruption that’s occurred in the media business. And so I was coming up
at a traditional media company, The Seattle
Times, and realized that there wasn’t much of
a web strategy in about the mid 2000s. They were still very much
wedded to traditional print advertising. And there were all kinds of
painful cuts and things going on. So I thought, I don’t think
this is for me long term. I was beginning to really
sink my teeth into biotech and specialize. I had done a fellowship at
MIT for science journalists for about a year. And that was sort of the
moment where it was– it dawned on me that
I could do this. I might need to figure out the
right structure online to do that, an Xconomy was that. I joined a startup, 2008,
and it was really focused on all things innovative. So the two guy and a dog start
up all the way up through the more interesting
projects , that, say, a big company might be
working on Alzheimer’s. And it was a great window
into the world of biotech. I didn’t have to worry about
the daily stock fluctuations so much. I could focus the science
and how it was being applied. And so I developed a following
as social media came on board. It became clear that I
had sort of what you might call a high affinity audience. I wasn’t going to reach the
largest number of people in the world with writing
about genomics or cancer immunotherapy. But there was a
small core of people who were very intently
interested in my subject material. So that– by the time
I was about to move on from Xconomy, 2014, I
was thinking that yes, I could potentially hang
out my own shingle as an independent media
entrepreneur focused on my biotech niche
and then I could layer in some of these
other things, like podcasts. Eventually, when I finally
got my book published, I could get that kind of in
the portfolio as different ways to reach people in the
information comments. KRISHNA YESHWANT: That’s great. So you started with the website
and then in the background were building the book–
or writing the book. Is that how it worked? Or how did you
actually start that? LUKE TIMMERMAN: I
started the Hood project while I was still at Xconomy. But I like a lot of
authors, I got to this point where I realized I’ve
done all these interviews, I’ve got all these documents,
it’s a mountain of material. I’ve got all my daily deadlines. When am I actually going
to write this thing? So I actually had to swallow
hard and say, you know what? I think I need to leave
my job if I’m actually going to write this book. Basically give myself a leave
of absence, which was almost a year to actually write the
book, finish it, get it edited, and then I started
the Timmerman Report. KRISHNA YESHWANT: I
see, so it was actually the book that prompted
you to take the next step. LUKE TIMMERMAN: Yeah. KRISHNA YESHWANT:
Great, OK, that’s real interesting, different
than what I thought. So let’s turn our
attention to the book. So as I read through it, one
thing that was striking– and as you know I actually
listened to it on audiobook, so I’m going ask you some
questions on that as well. But how did you come to
the idea of writing a book to begin with? Is that just the dream
of every journalist? Or is it– because I can’t say
that many of the folks that we interact with have actually
written such a long form piece of writing. And how did you
come to choose Lee, and how did the initial
interaction with Lee go? Because I can imagine it
being easy or challenging, because he’s such a
unique figure in this. How did it start? LUKE TIMMERMAN: Yeah,
so I was starting to get the urge to write a book
in the last couple of years of Xconomy. I had some experience writing
magazine type profiles of people. I thought– I enjoyed getting
to know people and their life story as a way of shining
light on the history of how technologies develop, really. And along in 2011 comes
the Steve Jobs book by Walter Isaacson. And I read this and
I thought, now this is a great example of what you
might call a living biography, because he was able to do a
whole series of interviews with Jobs for the last couple of
years when he was still alive. And so you could get
a lot of rich detail that you could never
get just from reading the documentary record. You supplement the record
with the interviews. And so this is a
big bestseller, too. So it was kind of inspiring. And I looked around and
thought, OK, I’m in biotech. Who do I know who has had
some kind of catalytic effect on this industry? And maybe not as
many aspects of tech that Jobs did, but
immediately thought of Hood. Now as you remember, I got
started at the Seattle Times and based there. And Hood had– I got to know him very early
on as a newspaper reporter. So I had a reporter source
relationship with him. I covered his Institute
for Systems Biology, which was sort of his next big idea in
the wake of the Genome Project, and various startup companies
he had been involved in. And I knew that there was this
tremendous force of personality and that he had a
signature achievement that I can explain to
anybody on the street, and that was that
he led the team that developed the first
automated DNA sequencer. So this was a tool that
revolutionized biology, we could say, with the
benefit of hindsight. And it was akin
to the development of the better, faster,
cheaper semiconductors that Intel developed. Gordon Moore and Bob
Noyce had that kind of catalytic and enabling
effect on technology. So I thought Hood
was a great subject. KRISHNA YESHWANT: When you– say you’d known him from
your time on the reporting side of it. How did you broach
that subject with him? LUKE TIMMERMAN: Yeah,
that’s a good question. Because so those
of you who’ve read the Isaacson book know
that it pulls no punches. There’s the good Steve and the
not so good Steve in there. And as an independent
journalist, that’s the kind of book I want write. That’s what I’ll
spend my time on. So I propose something
like this to Lee. KRISHNA YESHWANT:
Did you tell him there’s going to be a good Lee
and a bad Lee in this book? LUKE TIMMERMAN:
I told him that I would talk to your friends
and your enemies, your family. I want to tell the good,
the bad, and the ugly. I don’t know exactly what I’m
going to find at the outset, but basically you need to
put your confidence in me that I’m going to
be fair to you, that I’m going to do my
best to get it right. We aren’t always going
to see eye to eye. And it turned out
that at the time he had been thinking about
writing his own memoir. And it was kind of
a difficult thing, like was he going to
hire somebody to do it? And he didn’t really have time. And he sort of looked
and thought, OK, if you do this independent,
number one, more people are likely to
read it, because it won’t be sort of
the world according to Lee, a whitewashed version. And number two, I mean,
I think he had confidence in me that I knew the science
and could put it in context. So he agreed. Let the chips fall. I’ll agree to all the
interviews you want to do. I’ll open up my papers. So he was really good
at being cooperative. KRISHNA YESHWANT: So often
you hear about biographies in that format– and I think that was even the
case with Isaacson and Jobs where there was kind of a
tension or debate in it, but it sounds like he
was overall open to it and actually relieved
that he didn’t have to write the book himself. LUKE TIMMERMAN: There was that. I mean, but certainly
there were tensions. Especially getting
closer to the end, when you’re fact checking
some parts of the story that don’t jibe with
his version of events. And– KRISHNA YESHWANT: Can you
give us a couple examples? LUKE TIMMERMAN:
Well, so it might be hard for those who
haven’t read the book. But there’s a passage
in here in which I report on how he was ousted
as the Chairman of Biology at Caltech. And that was not
reported at the time. So when Hood left
Caltech in 1991, he was recruited by Bill
Gates to the University of Washington. And this was sort of like
the dawn of technology driven biology, biology
becoming more data driven, more of an information science. He and Gates shared this vision. And it was a big story when this
great scientist from Caltech came to Seattle. It was in the Wall
Street Journal. And none of the
underlying tensions of what really led to his
departure from Caltech were reported. Now, as a biographer
looking at these things in the documentary record
and interviewing people 20 years later,
you can dig deeper and get into more of the story. And that was
embarrassing and hurtful and there were times during
the fact checking process when Lee would
try to revert back to the so-called– the
cover story that Caltech was telling that enabled him
to save face at the time. So we had some tensions. We had some battles
over those things. KRISHNA YESHWANT:
One of the things I took away as I was reading
through the book is that there is this element to Lee that
I think is similar to some of the other great
innovators of our time, whether you think of
Steve Jobs you know or an Eric Lander, kind of
the variety of other folks that we all kind
of see in the media or in our companies and
whatnot, where there’s a bigger than life sort of quality. There’s a– this is the
grand vision of what we’re going to do, even
though it may not be clear how we’re going
to do it at the outset. As you spent time with Lee
and wrote the book and thought through– that came through in the
book, that there’s clearly that part to his persona. Did you find that
that was balanced by some other part where
it’s like, you know, he also did produce the
first automated sequencer. That’s a technical achievement. You know how much
of– to the extent that achieving great things
takes breaking through barriers and looking at the
world in different ways, in somebody like Lee, how much
of him is grander than grand, and how much of
it is, look we’ve got to make this stuff work. Is it 50/50, or just as
you dug into his persona, how much of it did you see? Or maybe there’s a
different framing to it, especially as you’ve
talked to some of these other entrepreneurs
who have those parts to their personas as well. LUKE TIMMERMAN:
It’s a great point. There really are so
common personality traits that you see in the people
that really shake up a field, and lead us to a new path. And it really is this single
minded intensity that– so first it is the vision. And he is a biologist,
first and foremost. This is where he came
from, his training, and he really wanted to answer
big questions about biology that you could not answer. Things like, how
is it that we are able to mount an infinite
number of antibodies in our immune
system to protect us from all these pathogens in
the environment– the viruses, the bacteria– when
we only have– we don’t have a gene for
every single one of those. Does that happen? They didn’t have
the tools for that. So he wanted the
answer, really bad. And he was dedicated to using– developing technology to run
bigger, broader experiments to gather the kinds of data
that you would need to answer a question of that magnitude. And he just– once he
developed the vision, he just had this single
minded intensity. And you can even see on the
cover photo of the book, that photo captures it. It’s like this guy
is in the zone. He’s like Tiger Woods lining up
for a putt, or Lance Armstrong in the Tour de France. There’s a focus, a purpose,
and nobody’s rules, nobody’s bureaucracy,
nobody’s sensitivities are going to get in
the way of that goal. That’s who he was. And so it was both his
great strength and at times a weakness. KRISHNA YESHWANT:
Yeah, I feel like we see so often that those two
things both change the world, but also can be painful
for the people around them. That must have come
out as you were talking to the people
surrounding Lee as well, just kind of the
inspiration that they draw, and perhaps some of the
challenges of working in the environment
that’s created in that. LUKE TIMMERMAN: That’s right. Yeah. He threw off a tremendous
amount of energy. Roger Perlmutter, who is now
the president of Merck research labs, had this great quote. And he said that,
Lee is like the sun. That throws off all of this
heat and energy, and he draws– he’s got this great
gravitational pull, he draws people into his
orbit, they’re stimulated, they do a lot of their best
work, graduate students and post-docs, but it can be a
little overpowering at times, and suffocating in some cases. KRISHNA YESHWANT: You invoked
the context of Gordon Moore and Intel and the
amazing work that was done to develop
infrastructure, these fundamental tools that– components that raised
the whole field. And I think that that
analogy runs true to the work that Hood did. As you think through the way
that the various instruments that Hood developed
unlocked biology, do you feel like we’re seeing
the full vision of what Lee had envisioned all the
way back then today, or do you still
feel like there’s a lot more to be unlocked? Clearly we’re seeing sequencing,
and all that sort of stuff, but there are other
components of the vision that you heard from him that
we’re still waiting to see? LUKE TIMMERMAN: Absolutely, yes. We’re still in the early days. And just for a little bit
of historical context– I mean, you know this since
you’ve read the book– but when Hood was
really emerging on the faculty at Caltech in
the 70s, the first manual DNA sequencing techniques
were being developed. And these were slow,
tedious processes. A graduate student would spend
his or her entire graduate school career and get a
PhD based on determining the sequence of just one gene. So five years– you
determine the sequence for making something
like insulin. Now today, you can
scrape up a skin cell and sequenced the
entire genome– the entire three billion
bases that are you and me– in seconds. Well, an entire
genome in, say, a day. But that gene would
happen in a split second. So he envisioned automation
coming to biology at a time when the tools were
very rudimentary and manual. And furthermore, there was
a technophobic attitude within biology. People in biology saw themselves
as kind of like high priests, and we don’t really
do the sort of thing that– we don’t make
widgets or tools. That’s the work of industry. And so Hood came in and
said, no, we need to do both. We need to develop
better tools to ask bigger and deeper questions. We need to gather
new kinds of data and turn it into a bigger
kind of information science. And he saw not just DNA
sequencing but other layers of information being crucially
important to thoroughly understanding the
whole organism. So he developed what they
called a microchemical facility at Caltech, where they
sequenced proteins, they synthesized
proteins, sequenced DNA, and synthesized DNA. Four instruments
working in harmony that would read and write in the
language of life, so to speak. And by looking at the different
layers of information, you could see how things
go awry and become diseased in a much more granular
fashion than you could before. KRISHNA YESHWANT:
Certainly sitting inside of Google, those four
components, you see– some of which have totally
transformed the industry, it feels like there’s still
more to come in it, certainly from a Google perspective, the
role that the amount of data that’s produced from
that set of instruments is clearly profound and
would suggest that there’s other infrastructure or other
tool sets that need to be built to manage it and help
get to that underlying ability or that ultimate
goal of reading and writing in the language of biology. How much of that part of it have
you seen Lee Hodd kind of focus on, having done all the
instruments, thinking about, OK, there’s all this data that’s
coming off these instruments– I think you referenced a couple
of things that he was doing– but where did that
that research take you as you were thinking
through, now that these instruments exist
or parts of them exist, what’s next? LUKE TIMMERMAN: Well it’s a
great question, because you can argue that we
haven’t yet reaped the dividends of the Human
Genome Project, and genomics, or information rich biology,
whatever you’d like to call it. I think we’re still very
much in the early days. We’re learning that
biology is even– as you peel back more and
more layers of the onion, it gets more and
more complicated. So the gene sequence
as you know, it’s not absolutely
deterministic. Just because you have
a genetic abnormality, doesn’t necessarily
lead directly to the path of disease. There are other points at
which proteins, cells, you need to get a more full picture. And we’re not there yet. And so there are efforts– in fact, Google’s
baseline project is one– to try to better integrate these
multiple layers of information from genes to proteins
cells, but also your observable phenotype
that’s in your electronic health records. And we have some challenges
with electronic health records in this country and
interoperability, getting different data sets to
line up and talk to each other. So that’s going to take
years to work through. KRISHNA YESHWANT: I
remember in the book, you described Arivale which is
a company that Hood had just, I think, got launched
maybe just as the book was coming to press. Any news about that? Anything that you’ve heard– because it seemed
like that was starting to get to some of these
questions around phenotype and how to tie all
this stuff together with the genetic underpinnings? LUKE TIMMERMAN: Yeah,
so for those unfamiliar, Arivale is a company– another startup company that
Hood has gotten involved with. And it’s trying to
bring about what he calls scientific wellness. So this is a big data
approach to your health. So they start with people
having their genome– their full genome–
sequenced, but once. Because that’s all you need. That’s a static
set of information. But then periodically,
say, once a quarter, you’ll get you’ll give
a blood sample or spit, and that will be analyzed
for the metabolites. So not all– what are the key
metabolites that are showing up in greater concentration
or another in your blood that might be sending
something awry? A signal of disease, perhaps. They also sequence
your microbile. We’re learning a lot
because of the tool that enables us to
sequence all the microbes in, say, a stool sample. You can get a sense of
one’s health– a snapshot. It’s constantly changing,
because the composition of your microbes is influenced
by your environment. So by gathering what he calls
a dense dynamic data cloud– so it starts with your genome,
the metabolome, the proteins, the proteome, the microbiome,
all these omic levels of information get combined. And hopefully by
gathering all of this they can see, say, a sign of– an early warning
sign of disease. So do you have something that
kind of looks like it might be pre-diabetes heading on the
road toward a more classic measurement of disease, like
your hemoglobin A1C being too high– you’re unable to control
your blood sugar. Can we see it? By gathering all of
this information, there’s going to
be a lot of noise. Can we find that signal? Can we apply computers
to identify disease at a point at which we can
intervene and potentially correct before it’s too late. And so they’ve layered in what
they call a wellness coach. So someone who works with– a computational a
biologist looks at the data and says, I think there
might be a signal here, tells that to a coach,
who is not exactly– sort of like a nurse
practitioner, who says, Krishna, I’m seeing
something kind of worrisome with
your blood sugar. You know you might want to lay
off the ice cream before bed. And if so, can we– when we check a
quarter after, can we see that that molecular
perturbation has disappeared and you no longer
look like you’re on the path to pre-diabetes? Now, this is really
pretty exciting stuff. But it’s not
exactly being done– it’s not done in the
traditional context of randomized controlled trials
that are the way at which we try to control for all
the variables that might be influencing our health. So there’s plenty of
skeptics out there who say, this is
kind of interesting, but it’s not giving
us definitive proof that what you’re doing
is really working. KRISHNA YESHWANT: I
did want to get back a little bit to the Seattle
and kind of the various sorts of geographies you see. I’ll turn to the
audience in a little bit and ask a couple of questions,
so queue some thoughts up here in a moment. But on your web
site, you mentioned that you’ve been through two
busts and 1 and 1/2 booms, I think, in the biotech sector. And I would assume that
we’re kind of still in the middle of a boom,
from your perspective. So maybe– I’d be curious to
hear your perspective on where we are in a cycle here, having
lived through a few yourself? But I’d also be really curious– I know you mentioned there
was a world when you started your career where
Microsoft and Boeing were the big industries in Seattle. Where Were things
today in Seattle? And how are you seeing
the various geographies that you spend time in–
the big ones that I think of are of course Seattle, the
Bay Area, San Diego, New York, Boston, do you
spend time in all these different geographies
and what are you seeing? Since you kind of,
perhaps more than most, have a spectrum of insight
across what various companies are up to in academics? LUKE TIMMERMAN: Yeah, yeah. So first question,
about the boom, yeah, I mean, we reached a peak
there in the summer of 2015, where there was kind of a
record number of FDA approvals, there was a record amount
of venture funding. The stock markets
were all riding high. And then came Martin
Shkreli, and some drug pricing controversies,
which scared some investors– thought, maybe
the presidential election will go some direction that might
clamp down on drug prices. So it fell down for a while. Now, in the last– this year, things have
rebounded to some extent. And we’re now back
on a track again toward pretty close to a
record number of FDA approvals. There are some
very exciting drugs which you know of, so I’m pretty
optimistic that things are– exciting things are
happening with regularity. A lot of it here
in the Boston area. Now, to the geography question. I mean, Seattle has been
utterly changed in the 16 years that I’ve been there,
the biggest one being the emergence of Amazon. They now have about
40,000 employees in the city of Seattle
and they plop them all just north of downtown. So there’s a tremendous
amount of bars and restaurants you know condos and street
activity that that wasn’t there in kind of a previously
rundown part of town. It’s brought a lot of growth. A lot of good economic growth,
but also some growing pains– traffic and housing prices. A familiar story to
many tech clusters. But as for biotech, I mean– I remain based in
Seattle, and there’s a terrific base of research
there at the Fred Hutchinson Cancer Research Center and
the University of Washington and a few other
nonprofits– the Gates Foundation is there
and leading the charge on infectious disease. But I get to Boston, and
San Francisco the most, because these are the
top two biotech clusters. So I’m meeting with companies
and scientists and investors in those two places quite a bit. San Diego as well, New
York once in a while. The way biotech has
grown as an industry, it does tend to
concentrate by geography around great academic research
centers, great hospitals, and then the money and the
entrepreneurs, and then all the service providers,
all of the consultants, the law firms, the regulatory
affairs specialists, everything that you need kind
of needs to be in one place. So that’s the way
it has evolved. KRISHNA YESHWANT: Let me
see if there’s any questions from the audience here. AUDIENCE: I was wondering
if you’ve looking at the new t-cell therapies
that are coming out– I’d heard one of them
got approved recently. I don’t know if you’ve
followed any of that. LUKE TIMMERMAN: Yes. Yes. So for those unfamiliar,
Novartis won FDA approval just a couple of weeks ago for
the first CAR-T immunotherapy, and this is a therapy in
which a patient with cancer, blood cancer, has white
blood cells withdrawn. They go off to a company lab. They use some gene
therapy to reprogram the receptors to recognize the
specific marker on cancer cells and then they
reinfuse those t-cells to go in and kill the cancer. And they have seen
extraordinary results in small groups of patients
with blood cancers. Something like 80%
complete remission rates in kids with acute
lymphoblastic leukemia. So this is a very
exciting development. I mean, we just don’t see
80% complete response rates in serious cancers with
traditional small molecule or targeted antibody therapies. So and furthermore,
we’re starting to gather a long
term follow up data. You need to say, yes
this is actually lasting. So very exciting moment. And there are lots of– there’s been an incredible boom. This is part of the story
of the last five years, is that immunotherapy has really
come to the fore in cancer. This is no longer like
a fringe science idea. It’s the main stage of cancer. Every company that’s in
cancer, every cancer center, is focused on how
can we redirect that power of the immune system
to go after the cancer cells. KRISHNA YESHWANT:
You actually have a feature on your web site,
Timmerman Report, if I recall, that was a review of every
company in the immuno space done alphabetically. And it was like, it was
pages and pages of companies, and I was like, this is amazing. How did you put that together? That seemed like just a
superhuman level of effort to put that amount
of data together. And I was looking
through it and thinking, oh my gosh, like the
only way to organize this is alphabetically, just
because every day there’s a new company in this space. LUKE TIMMERMAN: It
really is hard to keep up with all of the
scientific approaches, all the companies getting money. So yeah, I found myself
scratching my head and saying, how can I get a handle on this? So why don’t I just
go A to Z and try to find as many
companies as I could. And there were something
like 180 companies. And I just wrote short
profiles of each one of them back to back, along with
some links to primary sources where you might
be able to gather more specific
information on each one. KRISHNA YESHWANT: Almost as
many immunotherapy companies as there are video sharing
companies, I think, out there. [LAUGHTER] Are there any
questions out there? AUDIENCE: Sure, maybe just
two quick ones, one just about Lee Hood. I’m just curious that the
difficulties at Caltech back in the day, do
you think any part of that is the conflict between
sort of the new big science and what was sort of the
traditional RO1 science? LUKE TIMMERMAN: That’s a great
question, and absolutely yes. So Hood, because of the scope of
this vision, as it was really– as he was bringing in the
resources and the people to make it happen, his lab grew. He started colonizing more
and more space on campus. He was the chairman, and
he saw like all of this as being part of
his grand quest. Didn’t necessarily
pay a lot of attention to what the small science
people and the faculty– what their priorities were. And so he ended up– it evolved. When you have 60 or
80 people in a lab, and the guy down the hall has
five or six graduate students working on some very
narrow esoteric problem, it challenged the whole
culture of the way Caltech operated, or really any
university for that matter. The principal investigator
led model with five or six graduate students has been
around for a long time, and it’s given us a
lot of good science. So people in the small
science world looked at this and thought, what is this? I mean, how can you even
adequately supervise these people? Who are they? Are they tenure track faculty? Or are they like employees
of like a little company? Do we actually have
like a little company you know it’s kind of Caltech? It was strange. And it clashed with a lot
of the identity and the way Caltech really saw itself, as
this elite institution doing these rarified things. AUDIENCE: So just
as a follow-up, so now being across the street
from a place like Broad, that’s so amazingly
successful, do you see now, this many years later, after
Lee Hood’s lab at Caltech– you talked before about
how journalism has been disrupted by various changes. Do you see academia any
sense being disrupted? I mean, obviously it adapts,
it’s very smart people. But can you point
to like, oh, this is the trend that
I would like to see in terms of academic
straddling that line in biology between the large invention-type
laboratories of a Lee Hood, or this sort of thing you have
here in Cambridge versus what was more classic RO1
lead investigators? LUKE TIMMERMAN: I would say
that these two forms can now co-exist more easily. So small science is
still alive and well. Well, I mean, it has its
the model is still intact. I mean, there are challenges
to it, with the NIH budget constantly under pressure. But big science has
carved out more of a place for itself, big project driven,
that’s a little more industry like, occurs at a
place like the Broad, that’s fortunate enough
to attract philanthropy, that that can look a little
further out at a long term goal than, say, your classic
RO1 NIH age grant, which is more on a three to
five year time frame to show some results. I mean, but there’s a lot of
tension still between the two. I mean, = the whole
data sharing question. You know, a lot of
principle investigators, I mean, they make their
name in their field by getting published
in science and nature and not by dumping
all their raw data out in public databases
for other scientists to gather and learn
from in real time. So we have a serious time lag
problem in academic science. Now, big science still
has that cultural issue, but I think to a lesser degree. I’d be curious to hear your
thoughts on that, Krishna, but you know, you see some
cases of bigger institutions– I think they might be more
inclined to lead on this and say, like Daniel MacArthur
over at the Broad Institute, some of you may know. He’s got this
database for exomes– 60,000 or even more
collections of big data sets from 60,000
individuals who have had scans done on the
2% of their genome that makes code for proteins. That’s pretty useful and. He is actually able to advance
his career by putting this out in the open and then
letting other people share in that resource. So I think we’re
beginning to see some cultural changes between
small and big science, but change is hard. It takes a long time. Yeah. AUDIENCE: So to piggyback on
that last question, if you could look in your
crystal ball, looking into the future of biotech
based on what you know about Seattle now,
and how you said the landscape has fundamentally
changed because of Amazon? Do you think biotech could
or is moving to Seattle? I mean, San Francisco, Boston,
Cambridge are definitely hubs, but we’re becoming
crowded, very expensive. Is there room there? Is there a willingness
there to sort of expand beyond Amazon into
biotech, or do you think it’s going to stay– the hubs are going to stay
San Francisco, Cambridge? LUKE TIMMERMAN: I think
Boston and San Francisco are head and shoulders
above the other clusters, and will likely remain that way
as the rest of our lifetimes. There’s so much
historical momentum behind the basic research,
the clinical care, the venture capital, the history
of entrepreneurship, the human capital
pool that’s here. In a place like
Seattle, you have a few pieces of the puzzle,
but not all of them. You have the basic research
that’s world class. But– I didn’t mention this,
but when I started covering the industry, there was a
company called Immunex which developed the drug called
Enbrel, which was– still to this day,
20 years later, is one of the top five best
selling drugs in the world. It’s really a major step forward
for rheumatoid arthritis. Other drugs have come
forward since then, biologically enabled. And the company wasn’t
able to hold on to that. It ended up getting
acquired by Amgen, a lot of the assets and
people moved elsewhere. And so Seattle is like a lot
of these other hubs of biotech that doesn’t– it has some aspects of what
you need, but in this case, it doesn’t have the pool
of sales and marketing people, or executive talent,
that venture capitalists typically want to see
before they seed new things. And you have that in a place
like Boston, Cambridge. So you know– I’m sure Krishna has
no shortage of people that you can imagine running
startup companies here. KRISHNA YESHWANT: In Boston,
yeah, we’re surrounded by them. I’m curious, I mean, if you
were to zoom out a level and look at the biotech
industry over the time you’ve been covering it, there’s
the gigantic pharma entities you know that we all know the– Pfizers, the Roche the Mercks. There’s the small
companies that we finance and that are doing
exciting new science. Maybe some of them are public. Usually call it five billion
or under sort of market caps. And then we have kind of this
interesting array of companies like Vertex, Celgene,– I mean, Gilead, I mean
these have become– these are companies I think
we’ve seen go from startups to more mid-sized companies
to they’re becoming pretty large companies. And some of them have done
deals that are billion dollar acquisitions,
billion dollar deals, and they can kind of
do it without breaking too much of a sweat. If you were to dial the
clock forward, just given the context you’ve had
over all these years, you know what do you think
happens with those companies? Do you think they get
acquired by the big entities, do you think that they grow
up– a lot of them kind of, and I’m sure you’ve been
on the receiving end of all of their pitches
as they talk to you about various announcements,
they all have kind of I think the framework
of, look, we’re going to be the
next Merck, we’re going to be the next Genentech,
Roche, do you believe it? Do you believe that
those companies are going to grow into the
next big behemoths, or what do you think
happens with those folks? LUKE TIMMERMAN: You know,
it’s a great question. I think maybe it’s a
minority of the time– maybe 1/4 fourth of
the time those visions are realized by a company
that gets over the hump and develops a new drug. I mean, just getting one
drug over the finish line as an FDA approved product
and you know it really helping patients and getting
adequately reimbursed and making good money– I mean, very, very few companies
ever get through that funnel. And even fewer can do it twice. So this is a company
down the street, Alnylum Pharmaceuticals,
is a good example. So they’ve got RNA interference,
gene silencing technology. They did– they locked
up a lot of IP early on. They raised a lot of money. Brought in smart people. And 15 years later,
they just now have the phase 3
validating data necessary for treating one rare
disease which looks like that’s going to be a drug. Now they can start making money. But that really is
not enough for them to become an enduring entity. They need to do it at
least one or two more times to get diversified, like
a Celgene or a Gilead. Even Gilead and Celgene
have their diversification challenges. you look at how they
make their money, and often it’s one big
thing that does it. KRISHNA YESHWANT: I mean,
just to just call it out, I mean, even for the Celgenes,
the Gileads, the Vertexes, I mean, these are companies
that are actually pretty big, but to your point
like they still– they’re not fully diversified. And I guess that’s– maybe
that’ one of the questions, there’s the Alnylums, can they
make the leap into becoming a commercial organization? That’s something that–
I mean, obviously John’s a phenomenal,
phenomenal leader, you know you have
Agios, similar. And I think you were
an article about this, like this shift in culture
from being an early stage R&D company to becoming a
commercial organization– that’s its own challenge,
even after you have the successful drug
that’s been approved, can you kind of
convert the company into a commercial organization? When you look at these
next level of companies, the Vertexes, Celgenes,
the Gileads, which have maybe a small number
of assets that are producing huge revenues, do
you think that they will be able to get to
that diversification? Do you think there’s
just as much risk there as you see on the early
stage side of this? LUKE TIMMERMAN: Yes. I mean, it’s sort of
like the old saying, getting to the
mountaintop is hard, but staying there
is even harder. KRISHNA YESHWANT: Right, right. LUKE TIMMERMAN:
Regeneron Pharmaceuticals is one good example of a
company that’s now got, I think, six approved drugs,
and they’re laying the foundation for a genomics
based drug discovery, like really trying to link some
of these layers of information that I was talking about earlier
to try to create something sustainable, something
that can with some degree of predictability
and reliability roll off a new FDA approved
drug once every couple years. I mean, it’s still monumentally
difficult and expensive, and things are going to fail
for reasons that you can’t fully understand, even
after you’ve spent years and millions of dollars. But the companies
that I think are able to invest in enough
pieces of the R&D puzzle are the ones likely to endure. I think in Alnylum
and Regeneron, these are companies that have a
shot because of the investment in basic science. But often you see companies
where that’s not even the intention at all. They just– they take an asset
out of Pfizer that looks like it has some promise, and it
needs some focus development for maybe 10 years, and
that’s all the goal is, is to get that
one drug approved, sell it to a big
pharma company– KRISHNA YESHWANT:
Billions of dollars. LUKE TIMMERMAN: Reward
the shareholders, and then the management,
who is exhausted, will go sit on an
island somewhere. KRISHNA YESHWANT: Let me see
if there’s any other questions. I’ve got a couple of
others lined up here, but anybody else want to? AUDIENCE: You were talking
about the Seattle and Boston clusters in the US. What do you see around
the rest of the world as far as centers for biotech? LUKE TIMMERMAN: Yeah,
it’s a good question. So the UK has some
biotech infrastructure. Germany is another. Some in Japan. But the vast majority of new
drug discovery and development occurs in the US. There– of it I
think it comes back to the decades of investment
from the federal government, the NIH, in creating
centers of excellence. But also you have an
entrepreneurial culture, where it’s OK to gamble your
career on one of these projects and maybe fail, and as long
as you don’t defraud somebody along the way, maybe
you can try again. That’s part of our culture. We also have a
stock market that is very receptive and open to these
very high risk, high reward propositions. That’s not true
in other countries where there’s a
little more reticence around losing all of your
money, which does happen. So we could have a longer
conversation about this, but there are special
ingredients in the United States that have enabled
this to be the place where a lot of this activity occurs. And now, that’s not
guaranteed to last forever. I mean, we’re doing some
things like with immigration, for instance, that
could threaten our lead. It could for some of this
activity to go elsewhere. And it very well– some of the ingredients are
in place in other countries. They could– they’d
be happy to take it. KRISHNA YESHWANT: I
know you’re in town to do a bunch of things,
but as a venture capitalist, I’m obligated to ask you
about the panel you’re running later today about
how to avoid VCs and get the money you need. I actually think it’s
a phenomenal topic. LUKE TIMMERMAN: I thought
you were going to ask me about your portfolio companies. KRISHNA YESHWANT:
That’s coming next. We do that offline. But there is kind of this
interesting dynamic developing where there are new sources of
capital coming into biotech. And maybe it’s because we’re
in this boom cycle of it. But I think you’ve done
that panel in other settings or maybe– what are you seeing
out there aside from the traditional
venture approach to financing these risky,
crazy sort of companies? what. other sources of
capital or are there? LUKE TIMMERMAN: I think
you hit it on the head. The reason for this is that
biotech has had a good run. There were about
three years in a row where it outperformed the
S&P 500 and the NASDAQ composite index. So any time that happens,
you get more money flowing in and
saying, gee, I’d like to outperform the market too. And so traditional VC
has been around forever, and these are the folks who–
they raise money from pensions, endowments, limited partners– KRISHNA YESHWANT: Corporations. LUKE TIMMERMAN: Corporations,
and so they’re out there raising new funds
every few years. That’s one form– really the
dominant long lasting form– of venture capital. But there are all these
other types out there, like corporate venture capital. So GV is an example,
where you’re not out there raising money
from endowments or pensions. You’ve got some money
set aside, generally. I mean, they come in
different flavors, but some money set aside from
the parent company that says, we will gamble some of this
money on biotech startups. That’s just part of our mission. And some of them will pay
off and some won’t, just like any venture capital firm. But we have our
reasons for doing this. Then there’s also this emergence
of disease related foundations. So these are nonprofit
groups that in many cases have an interest in a
specific disease area, and they fund basic research. But I think in the last, say,
five to 10 years, a lot of them have recognized, well,
that’s not good enough. So if you’re, say, the Michael
J Fox Foundation for Parkinson’s Research, you can invest in
the bright researcher down the street at Dana-Farber
or Harvard Medical School, and that’s great. But their work is
ultimately going to lead to a published
paper in the New England Journal of Medicine. And again, that’s great. But it doesn’t go all the way
to a new Parkinson’s treatment. So how do you get there? Well, maybe you could
take some of your money and make equity investments in
a spinoff company that takes that asset out of that lab. And so many of
them have realized, can we set up this sort of
equity investment component within our charter? The Gates Foundation does this
for all kinds of immunology related companies that may have
an application for vaccines in the developing world that
the foundation cares about, but it also may be
useful for cancer. And that would be like
something that traditional VCs and corporate VCs can
all get together on. And you know so you’re
seeing disease foundations, corporate venture funds,
but also now family offices. So this is sort of the wealthy–
the billionaire phenomenon. Somebody like a Peter
Thiel, who says, gee, I’d like to start a company, a
biotech company, and that’s– all I need is a bright scientist
and a team of advisers. And what do you need?
$10, $20 million to run the next
set of experiments. Go give it a shot. So you’ve got a lot of
different kinds of new investing entities. KRISHNA YESHWANT: I’ve got so
many more questions for you. But I’ll ask you them probably
in another setting like this. Well thank you Luke
for taking the time to talk to us both in the
room and all the folks virtually here. You started things
off by saying that you could have gone to a variety of
different areas of journalism, and you picked this area
because all the exciting stuff and people in it. I think your book
does a phenomenal job of describing that. So many books in this space are
kind of a slog to get through. Yours was just a joy. So hopefully everybody
out there and in here gets a chance to
experience that. I thought the audio book
was phenomenal as well, but thank you for
coming and hopefully we get to do this more often
as you write more books. LUKE TIMMERMAN:
Thank you very much. Pleasure to be here. [APPLAUSE]

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