Dr. Eric Topol on Variants, Vaccines and AstraZeneca’s Data Reporting

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Marianne O’Hare : Welcome to Conversations on Health Care with Mark Masselli and
Margaret Flinter, a show where we speak to the top thought leaders
in health innovation, health policy, care delivery, and the great minds
who are shaping the hea lthcar e of the future.

This week Mark and Margaret speak with Dr. Eric Topol, Founder and
Director of the Scripps Translational Research Institute, a renowned
cardiologist with multiple patents to his name. He's become a leading
advocate in promoting pers onaliz ed genomic space medicine. Since
the pandemic Dr. Topol has focused on galvanizing input from the
digital health community to promote better national surveillance of
the path of COVID - 19.

Lori Robertson also checks in, the Managing Editor of F act C heck.org
and looks at misstatements spoken about health policy in the public
domain, separating the fake from the facts . We end with a bright idea
that's improving health and well being in everyday lives.

If you have comments, please e - mail us at [email protected] or find
us on Facebook , Twitter , or wherever you listen to podcast s . You can
also hear us by asking Alexa to play the program. Now stay tuned for
our interview with Dr. Eric Topol here on Conversations on Health
Care.

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Mark Masselli: We’re speaking today with Dr. Eric Topol, Founder and Director of the
Scripps Research Translational Institute. He’s the Executive Vice
President of Molecula r Medicine at Scripps Research.

Margaret Flinter: Dr. Topol has publis hed more than 1200 peer reviewed papers ,
multiple bestsellers, and is the Editor - in - chief of the health industry
publication Medscape. Dr. Topol, we welcome you back to
Conversations on Healthcare .

Dr. Eric Topol: Thanks, good to be with you both .

Mark Mas selli: You know vaccine distribution has been accelerating with Pfizer,
Moderna, and Johnson vaccines, all receiving swift emergency
authorization, but there are concerns about AstraZeneca ’s vaccine
and possible cherry picking of safety data that they supp ly to the
federal regulators and some possible side effects that we've all been
reading about in Europe. I wonder if you could just address the
AstraZeneca controversy and whether it might fuel distrust or
mistrust around other vaccines .

Dr. Eric Topol: Ri ght . Well, this is a very significant issue with respect to the cherry
picking of data. So what we understand and we're awaiting the final

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data is that the Data and Safety Monitoring Board, which is the same
one for all the vaccines, except for Pfizer, so called Operation Warp
Speed working with NIH, they were in constant communication with
AstraZeneca through the course of their United States trial. During
that trial, as it came to the end in March, the Data and Safety
Monitoring Board saw the final data s et and they said, that's what you
should be disseminating. But rather, instead AstraZeneca decided to
use the data from February 17, which is not the final data, it was an
interim analysis. It was incomplete. Based on the communications
that we know of now , the efficacy is not 79%, as was broadcasted by
AstraZeneca on Monday this week, and what we don't know is the
real number.

Now, the vaccine i s, I'm sure , is going to be efficacious. We know that.
But why would the company not give the right data . And th is is
unprecedented in my career as far as experiencing clinical trials . It’s
very disturbing and it undermines trust. So it's very likely that the EUA
will be granted in the weeks ahead by the FDA for this vaccine but this
was unnecessary. This was a kind o f self - inflicted damage,
unfortunately, and it's not the first time this company has done that.
There are issues that are beyond that. The one you mentioned with
respect to these rare clotting events that occurred in multiple
European countries and stirr ed a lot of concern last week, Germany,
Norway, Spain and others. These are rare likely vaccine induced
exceedingly rare. They are young, healthy people that get this very
low platelet count and then develop clotting that ’s quite diffuse multi
organ.

Now, this can occur with all the vaccines, any vaccine . It sets off an
immune response. The thing that is disturbing here is it looks like it
has slightly increased risk with this vaccine. And again, lack of
transparency, that's the theme . Instead of giving us a full disclosure of
all the cases and what happened so the medical community will have
complete confidence they didn't do that. They just said it's not related
to the vaccine or it's very rare. I'm sure it is exceedingly rare, but the
way to diffuse this is to provide the data and be transparent. So this
has been a problem with this particular vaccine manufacturer from
the inception of the program for COVID.

Margaret Flinter: Well, I think you're absolutely right, that transparency is what's critical
and in order for us to be able to communicate that to the people that
we're trying to get vaccinated, we have to have confidence in the data
so that we can give them assurance that that confidence is there. So
thank you for being so clear about that. One of th e big concerns that
we are hearing about , reading about , and that people are talking
about now, in our part of the country and I think nationally and really
across the world is the issue of the variants --- the UK variant now the
dominant strain in the US, c ertainly reading about what's happening

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in Brazil, cases across Europe spiking. What's most concerning to you
about the impact of variants in this phase of the pandemic? I dare I
say, we thought we had just climbed a little bit towards the top of the
hill and it looks like t he hill just moved ahead of us.

Dr. Eric Topol: Right . Well, this is the main topic of the day for the pandemic in the
United States, for sure, is what about these variants . The one that is
most concerning is this UK B117. The reason for that is, it's so highly
infectious . It has a higher lethality and it is, as you say, going to
become the dominant strain throughout the world and in certain
parts of this country it already has reached at greater than 50% a
cause of infection. Now, the go od thing is , we maybe able to fend this
off because the US has done a very good job with vaccinations , maybe
not perfect by any means but we have some 86 million people who
had at least one dose, which is more than one in every four
Americans . We have over 70% of the high risk group age greater than
65, who've had at least one dose. So we've done pretty darn well in
these months since late December. If we do fend off the B117 as far
as in not causing a big surge in cases, it'll be because of that, because
o n the other hand we've relaxed mitigation and many states have
opened up and the wron g thing to do at this juncture.

The good thing about that variant is it's highly responsive to vaccines.
The vaccines that are being used should or against it and that's kind of
the picture with the UK variant. The other variant, particularly the
South African variant and the Brazil, they are different . Their main
propert y is so called immune evasion. That is the vaccines won't work
quite as well, particularly the South Af rican one is more in that line.
But the transmission or infectiousness doesn't appear, at least at this
juncture to be as problematic. Now there are reports in Brazil, it could
be 250% or more. But that doesn't really make sense b ecause we
know the transmi ssion for the UK variant is about 50% increased, if it
was 250% increase for the Brazil variant, we would know it by now
around the world. So their main issue is re - infection for people
who've already had COVID. But they're not going to be out run by
B 117. That's the strain that's going to take over the world .

The one that can transmit the best is the one that's most fit and so
that's what we're going to see in the in the next few months. Now,
what about the New York variant ? What about other new variants ?
The New York variant appears to be more like the Brazil and South
African with this immune evasion property, not so much the high
transmissibility. We may see other variants because we still don't
have this virus in check. Remember, this is a worldwide sto ry. We're
seeing big surges in central Eastern Europe, and also in South
America, and even in Western Europe, in places like Italy and other
countries. So we're not over with this pandemic, the only thing that
we can do now is not relax mitigation and keep up with the aggressive

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vaccination and maybe we'll get through this. We're going to get
through it the question is when, and I'm still optimistic that by end of
Jun e, we'll be in very good shape.

Margaret Flinter: Great.

Mark Masselli: Well, that's good n ews. And really speaking of those variants , and
there have been a few recent studies that have been published,
they've shown a number of vaccinated patients are testing positive,
small numbers. I'm wondering that could be connected to this
growing number o f variants, you're talking about the B 1526 the New
York one and obviously the bigger one the B117 from England. I guess
perhaps it's just another reminder that even if you get the vaccine, it's
important to be vigilant with the public health protocols, as you were
saying, while vaccination efforts continue to scale.

Dr. Eric Topol: This so called breakthrough when you've had a vaccine and you get
COVID , so far it’s actually remarkable that it hasn't been associated
with symptoms. It's like the chance of you getting sick after the
vaccine. It's just remarkable. I take this moment just to point out a
paper that we wrote, Dennis Burton and I, Super Human Vaccines.
That's what this is . We're so lucky. I mean, I just can't even emphasize
this enough now that we h ave these vaccines with extraordinary
efficacy that are better than our immune system. Better, far better.
So the point is, if you just had COVID, you could get a re - infection. But
if you ’ve had the vaccine, the chances of you getting an infection , just
so symptomatic it so incredibly low. Now, you could harbor the virus
in your nasal mucosa and you could potentially not low likely, but you
could potentially be a carrier. But the chance you getting sick is it's
not nil but it's very low, very, very low. So these vaccines are just one
of the greatest triu mphs of biomedicine in history.

Margaret Flinter: Well, I really appreciate the absolute enthusiasm you have about that.
I think it's so true and I'm not sure that message has been broadcast
out there as loud ly as it should. So thank you for that. Along with that
c ertainly we need to celebr ate what the President has said, science is
bad back under President Biden, and we're seeing this with the CDC
and the way they're coming forth with their information. Certa inly
there was some erosion of confidence and trust in some of our vital
public institutions over the last year . What are you seeing coming up
in terms of how this administration is going to use the lessons from
last year to build a more robust public heal th infrastructure in the
country and to restore trust in science and in public health?

Dr. Eric Topol: Well, you know, it hasn't been all that long since January 20 th to now
and we've seen remarkable strides. The thing that I think about every
day is if we had the current administration a year ago, what kind of
different footing we'd be on right now, and we wouldn't have lost
over 530,000 Americans. So I see the restoration of trust is happening

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quickly and the funding for both the shunting of $200 million from the
government to the CDC for genomic surveillance, in addition to the a
good portion of the 1.9 trillion in the rescue package, these are things
that are going to help restore the public health ability to execute , to
support opening in schools, to su pport rapid testing, to support all the
things that we shouldn't have been doing a year ago. So I do think,
and the vaccination obviously, we've been relying on just tens of
thousands of volunteers throughout the country. But if we had that
better support, we could do better and go faster. So these are all the
things that we need to real ly take control of the pandemic, contain
the virus , and put it behind us, which we will, but fortunately we're on
the right path now.

Mark Masselli: We're speaking today wit h Dr. Eric Topol, Director of the Scripps
Research Translational Institute and editor of Medscape. His twitter
feed has become a trusted daily digest of scientific analysis around
COVID - 19. I'm wondering Dr. Topol, the pandemic has really
accelerated the p ac e of life science research. It often takes decades to
just a very short window. I'm wondering if you could just talk about
some of the remarkable scientific achievements that have been
realized. Certainly, you just were talking about the vaccine, but
mon oclonal antibodies, digital surveillance, telehealth . Has this cross
walked over into any other disease state or laid the foundation for
some promising research?

Dr. Eric Topol: Right Mark , well, I did write a short essay recently at Wall Street
Journal on that. I think what the points I was trying to get across or
just what you're alluding to. We've never seen a vaccine just get
developed in 10 months from the identity of the pathogen. Usually
that's average for the successful vaccines, eight years, and us ually the
review by the FDA is a year, n ot three weeks, and everything ha s gone
into a lightning speed, likes of which we've never seen in the history
of biomedicine. Now, the exciting part of this is that it not only sets
new standards or how fast we can move, but also like, for example,
the mRNA platform used for the vaccines can be used and is being
used to develop cancer vaccines, to develop autoimmune disease
interventions, and even ne rve degenerative intervention.

So we have now a whole new biotechno logy that's been validated
now used in hundreds of millions of people, which we didn't have
before. So th e spinouts here , it's kind of like remember how the NASA
program we learned all these things in space that ultimately change d
medicine like holter moni tors and everything, it's kind of the same
thing. We learned from the pandemic . We a re deriving so many vital
advances and speed, which used to be until now the average time
from an innovation to clinical practice use was 17 years, and we've
done that in l ess than a year. I mean, it's astounding . As a student of
medicine for over three decades I'm stunned by this every day and

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that's what really gets me enthralled about how the progress has
been made.

Margaret Flinter: Well, that's incredibly exciting. I wi ll say that the pandemic has maybe
overshadowed, I think, a little bit of the incredible work that has been
done over the last several years, and a project that you've been
guiding the All of Us Precision Medicine Initiative at the NIH, which
we've been pr oud to participate in and to learn from and to share
with people around the country. It seems to me that that project,
leveraging genomics and biometric data and AI, really focusing on
engaging people who have not, and communities have not always
been well represented in research, maybe ha d a lot to teach us in this
pandemic, as well, about how we engage people, how we gain their
trust, how we bring people in for a service or care or participation
where they might have been left out. I'm really curious, sin ce you sit
in so many positions of leadership across these communities, have the
lessons of the All of Us program informed some of the
recommendations about how we address the pandemic and also vice
versa, we've learned things in this pandemic, that will b e helpful in
the All of Us program, which for listeners who may not be as familiar
is a long ter m project that Dr. Topol leads.

Dr. Eric Topol: Well, the All of Us is most ambitious medical research program in
American history , pushing 400,000 participants to be followed for
dec ades ahead. What's interesting here is more than half are
underrepresented minorities and the real , I think, goal is getting every
one of these people to become citizen scientists, if they weren't
already. Now, during the pandemic, w e ’ve seen that again with
people with long COVID. They form peer groups, they are citizen
scientists . They’re participating not just in surveys but now with
sensors and testing whether or not vaccines will help them get out of
long COVID. So we're seeing a citizen science movement, which it
annotated all of us, but it's getting amplified now. It's really terrific to
see because we can engage with all these people remotely through
their phone, and we can get their data back to them. And we are all
basically democratizing medical information trying to help each other.
So we learn from it not just overall, but at the individual level, I think
that's really gratifying.

Mark Masselli: I want to pull the thread on a couple of things that we've talked
about, and yo u said, and certainly, we're in a different world than we
were last year. With the new administration, you've talked about their
commitment to science. Obviously, they're backing that up with
financial resources and more to come. Talk just a little bit now about
making sure that the BIPOC population, diverse population, our
country are represented in all the work that we do with the clinical
trials, spilling this sense of confidence and then just a few minutes
ago, you and I were chatting about sort of a vi sion for the future and

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healthcare. I wonder if you could just expand a little more on it. What
might that average citizen be looking at over the next three or four
years or be hopeful about as you think about this c onfluence? You've
been certainly a promo ter of telemedicine , telehealth , but talk about
how this inflection point that we're at now, how it might translate,
and it won't be that slow [inaudible 00:19:52] 17 years, but we might
see some rapid adoption. Paint that picture a little more for us.

Dr. Eric Topol: Well, I think the conduit is a smartphone and for people who don't
have a smartphone or don't have broadband internet, we should be
giving people a smartphone and data plans, because the phone and
years of data plans is cheaper than one night in the hospital or one
visit to an emergency room, which are average $5,000 to $2,000,
respectively. So we have to think smarter about using the technology
we have in Moore's Law that got us to this point . No one's really doing
that yet, but we should be d oing it. And so what I envision is that,
mobile phones aren't going away, they're just going to get even more
center stage for healthcare, and apps to help people manage their
condition or prevent their conditions. And so that's where we're
headed is .

We have to reach out to people that don't have technology, so that
every single American, if we're talking about the US, is on a level
footing with respect to access. That's how we reach them and that's
how we can get them vaccinated if they are willing . Ther e's so much
we can do once we use that Synapse and we know that people who
have these smartphones are totally relying on them for it's about food
and water in terms of necessity, we just have to get them to
everybody and we haven't done that. We still, may be 15 20% of our
populatio n doesn't have this technology.

Mark Masselli: Well, just note the FCC has launched a $3.2 billion for low income
people to get broadband, whi ch is going to be, we'll tell our listeners
more about it later , but in April it opens u p, which should go at the
heart of what you're saying, which is leveling this playing field so
everybody has that access.

Dr. Eric Topol: Yeah, this technology is never going to go away. It's just going to get
better with 5G and just faster and more data f low. I think it's time
now that we get everybody who if there's a problem of affordability,
we fix it. But these are small investments. When we're spending $2
trillion this is a tiny line item. It just befuddles me that we haven't
done this, when you think about the cost of American health care,
which is astounding. So I hope we'll see that come along.

Mark Masselli: But I dare ask the question. What publication are you are you worki ng
on right now that might hit?

Dr. Eric Topol: Well, we have a long COVID one coming out hopefully soon about ,

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people that develop a very fast heart rates for months. They go from
70 to 100 and so in addition to their symptoms, they have physiologic
objective signs that are --- we're going to learn a lot more about long
COVID. It' s a big residual of our inadequate efforts last year . The cases
of long COVID it may be 10% of the 30 mil lion confirmed cases, at
least.

Mark Masselli: What's your sense just about the pediatric, t he need for pediatric
vaccines?

Dr., Eric Topol: I think it 's essential, even though they don't get sick very often,
they're still carriers and there's still some who do get sick and get that
MISC, horrendous condition, even though it's exceedingly rare. So we
have to get everybody across the board hopefully kids ’ vaccine wor k
will get done pretty quickly.

Margaret Flinter: We've been speaking today with Dr. Eric Topol, Director of the Scripps
Research Translational Institute, the editor of Medscape, author of
several bestsellers including The Patient Will See You Now. Follow his
work by going to drerictopol.com or follow him on Twitter
@EricTopol. Dr. Topol, we want to thank you for being a lighthouse in
this pandemic storm for being a voice of trust of reason and science,
and for fostering collaboration across the global scientific community.
And thanks for joining us once again on Conversations on Health Care.

Dr. Eric Topol: Thanks very much Margaret and Mark, great to be with you.

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Mark Masselli: At Conversations on Health Care we want our audience to be truly in
the know when it comes to the facts about healthcare reform and
policy. Lori Robertson is an award winning journalist and Managing
Editor of FactCheck.org, a nonpartisan, nonprofit consumer advocate
for voters that aim to reduce the level of decep tion in U.S. Politics.
Lori, what have you got for us this week?

Lori Robertson: A Food and Drug Administration presentation on monitoring the
safety of COVID - 19 vaccines listed possible adverse events the agency
might track . But an Instagram post misrepre sents the document ,
falsely claiming it shows the vaccines are known to cause harmful side
effects including death. It's just one example of misinformation about
the COVID - 19 vaccines that is circulating on social media. The popular
Instagram post cites a government document to falsely claim that
federal officials know that the COVID - 19 vaccines cause death and
other dangerous side effects. But the post is wrong. The FDA
presentation on its sites, which is publicly available doesn't say that
and there is no evidence that the COVID - 19 v accines have caused any
deaths.

The FDA presentation was given at an October 30 meeting of a CDC

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Advisory Committee. The presentation outlined a variety of ways that
FDA ’s Center for Biologics Evaluation and Research would mon itor
vaccine safety once COVID - 19 vaccines were available. One slide in
the presentation showed a “ working list of possible adverse event
outcomes ” . These are outcomes the FDA could possibly monitor once
a vaccine was authorized. Daniel Salmon, Director of the Institute for
Vaccine Safety at Johns Hopkins University told us, officials develop a
list of adverse events to monitor in order to proactively ensure the
vaccine rollout is safe. And there's a difference between a report of an
adverse event following immunization and an adver se event caused
by the vaccine, he said.

Anyone can submit a report of an adverse event that occurred after
immunization through the vaccine adverse event reporting system .
With more than 109 million doses of COVID - 19 vaccines ad ministered
in the US as of March 15, the CDC received 1913 reports of deaths
that took place aft er someone received the vaccine. On March 15 , the
CDC said that none were linked to the vaccination. “ A review of
available clinical information including death certificates, autopsy and
medical records revealed no evidence that vaccination contributed to
patient deaths ”.

That's my fact check for this week. I'm Lori Robertson, Managing
Editor of FactCheck.org.

Margaret Flinter: FactCheck.org is committed to fact ual accuracy from the country's
major political players and is a project of the Annenberg Public Policy
Center at the University of Pennsylvania. If you have a fact that you'd
like checked e - mail us at www.chcradio.c om , we'll have
FactCheck.org's Lori Robertson check it out for you here on
Conversations on Health Care.

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Margaret Flinter: Each week Conversations highlights a bright idea about how to make
wellness a part of our communities and everyday lives. Wh en ventu re
capitalist and Shark Tank co - host Mark Cuban decides to sink a couple
of hundred thousands of dollars into your business idea, you're
probably onto something . That's what happened to Olivier Noel, a
medical student and young geneticist at the Un iversity of
Pennsylvania , when he appeared on the popular ABC show . Noel
learned that no matter how many resources a clinical study has, it is
still extremely difficult to get a large sample of participants to join in
studies, especially ethnic diversity. So he thought, what if you could
eliminate the barriers to research participation and build up a rich
DNA database for future research all at the same time, and he created
DNAsimple .

Olivier Noel: I think the idea came about right on my second year of my P hD . I was

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sequencing ability, there was enough funding for a really amazing
research projects, but ended up being a little bit of a chasing game,
where we couldn't build strong enough co des at first . Some of the
patients we were looking for, it was taking a very long time for them
to come. And so I ended up going to a genetics conference and the
keynote speaker there was alluding to a similar problem. One of the
ways they were able to contact patients was through Facebook. So,
the joke at the time at the co nference was that, Facebook is the new
way of doing genetics. So I wanted to sort of leverage the Internet and
particularly leverage social media to be able to build a national
database where somebody did not need to be a patient to be able to
participate in this resea rch study.

Margaret Flinter: All the participants have to do is to take a simple swab of the inside of
the mouth, send it in and wait to see if your specific DNA is of interest
to researchers. Noel says that the company will make their DNA and
disease data available to researchers studying specific diseases,
offering those researchers a much broader spectrum of study
participants.

Olivier Noel: So one of the things we really wanted to do with DNAsimple is to
allow for the possibility of doing l ongitudinal study so that you keep
continue keeping contact anonymously, obviously with a particular
donor. If you're doing a study for example, and you have the ability to
collect samples now, collect samples in three months and see how
that varies, which is very difficult to do if you are going to be in
contact with a patient once.

Margaret Flinter: The study participants themselves receive an extra something for
choosing to participate a cash stipend for of fering up their DNA to
research.

Olivier Noel: S o we ultimately provide a minimum of $50 every time somebody
provides a saliva sample.

Margaret Flinter: DNA simple a vetted database linking researchers with a broad array
of participants to enhance lab research by eliminating the barriers to
f inding parti cipants , now that's a bright idea. .

[ Music ]

Mark Masselli: You've been listening to Conversations on Health Care. I'm Mark
Masselli.

Margaret Flinter: And I'm Margaret Flinter.

Mark Masselli: Peace and Health

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Marianne O’Hare : Conversations on Healt h Care is recorded at WESU at Wesleyan

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University, streaming live at www.chcradio.com , iTunes, or wherever
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