0:04

I will say that I

0:07

was a science nerd from a

0:09

very young age. I actually have sitting

0:11

in my office at work, tiny

0:14

little child's microscope

0:17

that I was given as a gift when

0:19

I was, you know, very very young. And I

0:21

was that kid. You know, if

0:23

I cut myself, I would

0:26

run into my room and put some

0:28

of the blood on the slide and see. I didn't

0:30

know what I was looking at. I don't think the microscope

0:32

was even strong enough to really see anything, but

0:34

the interest was there. That

0:39

was Dr Jill Holland Back, an immuno

0:41

geneticist at the University of California,

0:44

San Francisco. Today,

0:46

that former self described science

0:48

nerd leads research into

0:51

one of the mysteries of COVID, specifically

0:54

why some people get the disease but

0:56

show no symptoms, and what

0:59

that can tell is about treating

1:01

and preventing it. I'm

1:03

a land ververe In. This is Seneca's one

1:06

Women to Hear. We are bringing

1:08

you one hundred of the world's most

1:11

inspiring and history making women

1:13

you need to hear. For

1:16

years, Dr Hollandbach and her

1:18

team at the Hollandbach Lab

1:20

have focused on a set of genes called

1:23

h L A and h l a's

1:25

relationship to autoimmune diseases

1:28

like multiple sclerosis. But

1:31

since the pandemic, the Hollandbach

1:33

lab has turned its attention to COVID

1:36

as well. Their answer

1:38

to the question of symptomless COVID

1:41

may lie in the genetic mutation of

1:44

h l A. Listen

1:46

and learn why. Dr Jill Hollandbach

1:49

is one of Seneca's One Women

1:51

to Hear. I'm

1:56

speaking today with immuno geneticist

1:58

Dr Jill Holland and

2:01

we're going to discuss her research on

2:03

COVID. Welcome, Dr Holland Beck.

2:05

It's really wonderful to have you with us. I

2:07

know our listeners are going to be very interested

2:09

in this topic. Thanks so much

2:11

for having me. Now I understand

2:13

your leading research into who

2:16

does and who does not get

2:18

COVID well, I first

2:20

of all, I want to say that we're

2:23

really focused on people who have

2:25

tested positive for the virus that causes

2:28

COVID but never had symptoms. So

2:31

for those who actually have

2:33

had the COVID virus but don't

2:35

show any symptoms, why

2:38

is that? Is it a genetic mutation?

2:41

We think so, not probably

2:43

not everybody, but in a proportion

2:47

of the individuals that we've studied,

2:50

it seems that a specific version

2:52

of an immune system gene that we're

2:54

interested in generally in my lab seems

2:57

to make them much more likely to be symptomatic.

3:01

So perhaps you can tell us more

3:04

about precisely what you're

3:06

looking at in your research or their implications

3:10

in terms of genetic mutation. What

3:12

can you tell us about what you've learned? Sure,

3:15

so my lab is generally

3:17

interested in a

3:19

set of genes called h L A, human

3:22

leukocide anergen and I

3:24

think a good way to think about it is to

3:26

think about the transplant

3:29

settings. So when we talk about matching for

3:31

a transplant, these are the genes that we match

3:33

on. And in fact two

3:36

UM one major

3:38

component of our study involved going

3:41

back to individuals who are registered

3:43

as potential bone marrow downors and asking

3:45

them about their COVID experience, because we

3:48

already have data on the genes of

3:50

interest for them. So h

3:53

L A or genes that encode important immune

3:55

system molecules,

3:57

and the job of those molecules is

4:00

to present or show

4:02

to UH your effect

4:06

or cells, your T cells in your immune

4:09

system, pieces of foreign

4:11

anigen or peptide, pieces

4:14

of protein. Is probably a better way to put that

4:16

better derived from things like viruses

4:19

and bacteria, and then the

4:21

T cells come along and they inspect

4:24

those pieces of foreign protein and

4:28

generate an immune response if it's something

4:30

that is not supposed to

4:32

be there. So the

4:34

interesting thing about h l A is

4:36

that they're extremely variable

4:39

between people, between populations.

4:42

So most genes

4:44

have maybe one or

4:47

a few different versions

4:49

that we refer to as a leal. H

4:52

l A has literally thousands and thousands

4:55

of different versions that

4:57

we see, you know, across the globe,

5:00

and that's why it can be so hard to match somebody

5:02

for a transplant, because one person's

5:04

h l A looks very different from another

5:07

person's h l A. So

5:10

what we and and many others

5:12

hypothesized, you know, very early in the

5:15

pandemic, was that different versions

5:17

of these genes, because they're so

5:19

important in the immune response to pathogens,

5:22

might be important

5:25

in differential response to the

5:28

virus that causes COVID nineteen

5:31

and so we went out to start

5:33

looking for individuals

5:36

who had tested positive. Because

5:40

the important thing in studies like this is

5:42

that it's very hard to control for exposure,

5:45

so it's very hard to ask the question does

5:47

somebody who gets

5:49

infected and who doesn't. Because there's so

5:51

many variables in whether

5:54

somebody is exposed to the virus, what kind

5:56

of mitigation you know, are they have, they've been

5:58

masking, and things

6:00

like the humidity

6:02

in the room at the time of exposure. There's

6:05

far too many variables for us to really

6:08

say for certain that somebody has or

6:10

hasn't been exposed, or that

6:12

their lack of infection is due

6:14

to something genetic. But what the

6:16

question that we can ask is,

6:19

when somebody has a confirmed infection,

6:21

they've tested positive for the

6:24

virus, what

6:26

does their disease course look like compared

6:29

to the person next to them? Because we

6:31

know that there's a huge range of disease

6:33

course, everything from asymptomatic

6:35

disease to you know, extremely

6:38

bad outcomes, people becoming hospitalized,

6:40

ventilated, and you know, we've

6:42

had you know, tragic number

6:44

of deaths, and so what

6:47

we want to know is what mediates

6:51

that? What you know, what is

6:53

there something biological, Is there's something genetic,

6:55

No, is there's something about their h l A that

6:58

changes how somebody responds to

7:00

the infection. And a

7:02

lot of the studies up to this point

7:05

that have been done thinking about not just h

7:07

l A, but genetics in general have really focused

7:09

on the severe outcome

7:12

end of the spectrum. And there's really good reasons

7:14

to do that. You know, people have gotten really

7:16

sick. We want

7:18

to understand why we want to

7:20

prevent that. Some of the reasons

7:23

that those have been the

7:25

patients who have been focused on are practical

7:28

because when people are in the hospital,

7:30

you're more you know,

7:33

it's much easier to get

7:35

samples, biological samples like blood

7:37

and DNA. But really,

7:41

you know, the vast majority of

7:43

people who experienced infection do not

7:45

wind it in the hospital. They

7:48

have you know what we would term, you know, relatively

7:50

mild to moderate disease. And we were kind

7:53

of interested in those people, and specifically

7:55

the subset of people who just don't

7:58

have symptoms at all, not a stuff,

8:00

he knows, not a scratchy throat, nothing,

8:04

And so we asked that question

8:07

individuals who have in

8:09

infected with the virus, did

8:11

you or did you not have symptoms? And

8:15

what we found was this extremely

8:17

strong effect of a particular

8:19

version of one of the h l A genes

8:21

called h l A B that seems

8:24

to really enhance somebody's

8:27

chance of not having symptoms

8:29

when they're infected with the virus.

8:32

So fascinating, and

8:34

can that be determined in advance

8:36

for somebody to know if they've got

8:38

that makeup that they're going to be

8:41

symptomless. Well, first of all, I

8:43

want to be clear, just because you

8:45

have this particular version of this gene,

8:48

so the gene is called h L A B and

8:50

and the version that we're interested in is called h

8:52

L A B fIF one doesn't

8:54

mean that you absolutely will be asymptomatic.

8:57

It just means that you're probably

8:59

too to three times more likely to

9:02

be asymptomatic. So I

9:04

think that it doesn't necessarily

9:07

ensure that you would be. I don't know that

9:09

it would be particularly helpful for somebody to

9:11

know that it's UM. It's not

9:13

a test that's done commonly, unless

9:16

somebody happens, for example, to be a

9:18

volunteer bone marrow donor they

9:20

might know their type. But I don't

9:23

know that that would be a particularly

9:26

useful thing for somebody to know. I

9:28

think that you know. For me, it's

9:31

more about what this

9:33

finding tells us about the

9:35

immunopathology of the disease

9:38

and what kind of directions it can point

9:40

us to. In terms of possible

9:43

vaccine design and possibly

9:46

treatments. So this is ongoing

9:48

research as you keep probing

9:51

and coming to various conclusions

9:53

along the way. Absolutely, So

9:56

you know, after this initial finding we

9:58

went back to the lab. We've since

10:01

um and we're in the in the middle of writing

10:03

this up right now, so I'm hoping that this

10:05

paper will be released fairly

10:07

soon. But went back into the lab

10:09

to understand first of all, can we detect

10:12

this in in other patient cohorts

10:15

UM? And also you

10:17

know, what is the the actual

10:20

um functional activity

10:23

of T cells in these individuals. So that's

10:25

that's something that we've been looking at carefully. And

10:28

UM have some really interesting new

10:30

data on senecas

10:34

one hundred women to hear. We'll be back after

10:37

the short break. You

10:48

had a research team called

10:50

the Holland Buck Lab. Are

10:52

there other scientific questions besides

10:54

those you've just been describing that

10:57

you're looking at as well trying to answer?

11:00

Sure? So, my lab at UCSF

11:02

is broadly focused on immuno

11:05

genetics in human health and disease,

11:07

So that mostly takes the form

11:09

of us thinking about these h l A genes

11:12

and UM. So, for example,

11:14

one of the reasons that I'm in the Department

11:17

of Therology at UCSF is

11:19

that a particular version of h

11:21

l A is also the most

11:24

important predisposing

11:26

gene in multiple sclerosis. And

11:29

we've examined a number of neurological

11:31

diseases from the point of view

11:33

of this gene system Parkinson's

11:36

disease, my skinia gravis

11:38

for example. So that's ongoing

11:41

work that we're focused on. We're

11:43

very focused in on multiple sclerosis

11:46

in my lab, and we're also

11:48

interested in other common

11:50

elements and and how different

11:53

versions of h l A predispose

11:55

somebody or or protect them from

11:58

common illnesses as

12:00

well as ubiquitous viruses

12:03

like megalovirus. So

12:06

we're asking those questions all the

12:08

time in the lab, and that's

12:10

really the main focus. And we were doing

12:12

that long before COVID, but you

12:15

know, once the pandemic came around, we absolutely

12:18

refocused a lot of our energies, as

12:20

did so many others, to ask

12:23

these questions well. And they're so

12:25

important obviously because they affect

12:28

just so many people who still don't

12:30

have the answers they'd love to have, right

12:33

right I you know, I mean, on the one hand,

12:35

it feels like it's been a long time, and

12:37

and how are we still here? And why are we still

12:40

worrying about this? Nobody I don't

12:42

think anticipated this was going to go on for so

12:44

long. But you know, another way

12:46

to look at it is there's just been

12:49

incredible, remarkable progress

12:52

made in a very short period of time.

12:55

I'm completely blown

12:57

away by, you know, the amazing

13:00

work that's been done all over the

13:02

planet trying to understand this

13:04

disease. And it's really just been an

13:06

incredibly impressive scientific

13:08

feat But I think that, you

13:11

know, people like me and and

13:13

my colleagues are just incredibly

13:15

motivated because we're the same

13:17

as everybody else. We've experienced the pandemic

13:20

the same as everybody else, right, And you

13:23

know, I first started putting

13:25

together the project to look at this like

13:27

so many other people, sitting you know, in

13:29

my home office on lockdown.

13:32

So I think there's you know, a lot

13:35

of motivation across biomedical

13:37

science to answer these questions. Well.

13:40

And I think that's that's true about

13:42

your mentioning MS as well. So

13:45

many people are afflicted with that absolutely,

13:48

yeah, And it's an extremely debilitating

13:51

disease and impact you

13:53

know, people in the prime of their lives.

13:56

So you know, in

13:58

general, this is just extreme, really

14:00

gratifying work to do. And you

14:02

know, I feel like I've been really fortunate to have

14:04

been able to focus my

14:07

my work life on on solving

14:09

these problems. It definitely

14:11

helps me to feel a little bit less

14:13

helpless in the face

14:16

of what we've all experienced.

14:18

Well, it's certainly critically important.

14:21

Can we talk about you a

14:23

little bit you personally? I

14:26

know you're an you know, geneticist.

14:29

What does that mean. I mean, it's a big

14:31

word, and I'm sure our listeners are

14:33

wondering what does she do or what

14:35

does that field represent? Sure,

14:38

so it's really a sub

14:40

field of genetics. I trained as

14:42

an immunologist. Um I

14:44

did my PhD in immunology at Berkeley,

14:46

but I did my training during that

14:48

time in a genetics lab, and

14:50

so it's a sub field of genetics

14:53

where we're focused specifically on

14:55

these very variable immune

14:57

response genes. And it really

15:00

acquires an entirely different

15:02

way of approaching genetics

15:04

and thinking about genetics because of the high levels

15:06

of variation, but also because it's

15:09

so important to consider the structure

15:12

and the function of the immune molecules

15:14

while we're thinking about the

15:16

genetic aspect. So

15:18

it's a sub field that's

15:20

generally um focused

15:22

on things like transplant and autoimmune

15:25

diseases, but it really has

15:28

um kind of far reaching

15:30

applications that

15:32

is certainly wonderfully rewarding.

15:35

It sounds like to be able to explore

15:37

these areas. How did you get interested

15:39

in this field? Was it your upbringing?

15:42

Was there a moment when you really

15:44

set to yourself, I want to be a scientist.

15:47

Yeah. I will say that

15:49

I was a science nerd

15:52

from a very young age. I was interested

15:55

in scientific things

15:57

as far back as I can remember. I actually

15:59

how of sitting in my office at work,

16:03

tiny little child's microscope

16:06

that I was given as a gift when

16:08

I was, you know, very very young, and I

16:10

was that kid. You know, if

16:12

I cut myself, I would

16:15

run into my room and put some

16:17

of the blood on the slide and see. I didn't

16:19

know what I was looking at. I don't think the microscope

16:21

was even strong enough to really see anything, But

16:23

you know, I was the interest was

16:26

there. I used to you know, graph

16:29

the details from my doctor's appointments

16:32

and things like that. But you

16:34

know, actually, when I was growing up, I

16:36

didn't really understand

16:39

that being a scientist was a job.

16:42

I grew up in a you know, in a

16:44

Jewish family, where if

16:47

you were interested in science, you became a doctor. If

16:49

you're interested letters, you became a lawyer. And those

16:51

were the only two options

16:54

that were presented to me. But you

16:56

know, during the course of my

16:59

education, I really kind

17:01

of fell in love with immunology.

17:03

That was during a period of time when I was working on my

17:05

master's degree in public health. At

17:09

the time, I had actually been interested

17:11

in going into women's health and health

17:13

policy. I had gone to work for Planned

17:15

Parenthood straight out of college. UM,

17:17

but I got a little bit sidetracked and fell

17:20

in love with immunology. And then during

17:23

the course of my PhD, I was particularly

17:25

interested in h l

17:27

A because my mother had rheumatoid

17:29

arthritis and h l A is very important

17:32

in autoimmune disease and including

17:35

room toid arthritis, and that kind of sparked

17:37

my interest and had an opportunity

17:39

to work in a lab that was focused

17:42

on these genes. And it's

17:45

um, it's been quite a long time. The

17:47

rest is history. Here I still

17:49

am doing important work. Did

17:51

your parents nurture your interest

17:54

as a child in science or were there mentors

17:57

along the way who inspired

17:59

you. I think you know, my parents,

18:02

Um, my father was

18:04

was a c P A my you know, my

18:06

mom had been an English teacher. They were

18:09

not really stem people, so

18:12

um, you know, they encouraged

18:14

me, of course, but I think, you know, to

18:16

be honest, you know, to the day

18:19

my dad died, he

18:21

used to variably describe me as a microbiologist.

18:24

You know what of this that he never

18:27

you know, he tried but didn't really

18:30

understand what I was doing. But I

18:32

certainly, you know, I had some great

18:34

teachers along the way. I had

18:37

a physiology teacher when

18:39

I was in high school who really sparked

18:41

my love for that topic, and I went on to become

18:43

a physiology major at Berkeley.

18:46

And then some you know, really key

18:48

professors during during my time at

18:50

Berkeley's so um,

18:53

yeah, some great mentors along the way,

18:55

and um peers and colleagues

18:58

as well who have been extraored, early

19:00

supportive through the years. Well,

19:02

here at Seneca women we often emphasize

19:05

how important it is to have women in

19:07

science, and we still have to

19:09

do better in that respect. I think you agree

19:12

as a general proposition, but I

19:14

wonder what you think about

19:16

why having a women's perspective

19:19

is important in your field if it is,

19:22

well, I guess what I would say is, I don't

19:24

know that as a woman, I necessarily

19:27

have a different perspective, at least not on the science

19:30

necessarily. But you know what, as

19:33

a professor at a research and university,

19:36

part of my job is to train the next generation

19:39

of scientists, and I think that

19:41

that's where, you know, having representation

19:45

is really just so important. I

19:47

think that, um, you

19:49

know, we bring to the table a

19:51

different set of life experiences,

19:54

UM, A different way of

19:57

having experienced the world and

19:59

moved through the world, and

20:01

that is really, um

20:05

I think an asset when we're

20:07

training not just you know, the next generation

20:09

of women's scientists, but the entire next

20:11

generation of scientists. I think that having

20:14

that different perspective on you

20:16

know, life and

20:19

and life experiences

20:21

is extremely important and

20:24

helpful, UM as as we

20:26

train young scientists. Well,

20:29

I always hate this moment looking

20:31

at the clock when we're nearing the end

20:33

of a fascinating conversation, but

20:36

I really would like to ask you before

20:38

we have to take leave. You know, given

20:41

that we've all collectively gone

20:43

through a couple of years now

20:45

of the epidemic. We've been

20:47

talking about COVID, We've been talking about

20:50

other viruses. Certainly there

20:52

are more on the horizon we haven't named

20:54

or don't know anything about because there

20:56

yet at the development stage,

20:59

probably, But given all

21:01

that, what makes you optimistic? What

21:03

gives you hope? Because this is tough

21:05

stuff, it is. But you

21:08

know, as I said earlier, I

21:10

realized it feels like it's it's been a

21:12

long time, and that it's

21:14

been you know, one step forward,

21:16

two steps back through the pandemic.

21:18

But you know, from where I sat,

21:21

I'm just absolutely marveling

21:26

at the progress that we've made. And

21:28

it's really been an

21:31

incredible experience to be

21:35

in the middle of these

21:37

research efforts and to look

21:39

around me and see my colleagues

21:41

at UCSF and across the country

21:44

and across the world who have really

21:46

come together in I think

21:48

a unprecedented

21:50

way. And I'll say that the levels

21:53

of collegiality and collaboration

21:56

that I've experienced, you know, particularly

21:59

working on this topic, have

22:02

just been so heartening. Um

22:05

I think that there's

22:08

often a lot of um, you know,

22:10

competition and science and

22:13

you know, trying to be very protective

22:15

and and get ahead because you know, just like

22:17

everybody else, we have careers that we're trying

22:19

to promote and move forward, and

22:24

that's really a lot of that has

22:26

fallen by the wayside during the pandemic,

22:29

and the the level

22:31

of collaboration has

22:34

has been really something to behold.

22:36

And I think that the proof is

22:38

in the pudding the

22:41

strides that we've made. I mean, if if

22:43

you just think about the vaccines alone,

22:45

I mean, it's it's really just

22:47

an absolutely incredible scientific

22:50

accomplishment. But that's really

22:52

just you know, the tip of the iceberg.

22:55

What we've learned in the last two and a half

22:57

years is absolutely

23:00

mind blowing. And so when I

23:02

think about what comes next,

23:04

I mean, there's there's always going to be challenges.

23:06

I really hope there's not going to be another challenge

23:10

of this magnitude in my lifetime, but

23:13

but who knows. But when

23:15

I see how

23:18

folks really apply their expertise

23:21

and come together to solve these problems, and it

23:23

makes me very hopeful that we'll be able to

23:25

deal with whatever comes next. Well,

23:27

thank you so much, Dr Jill

23:29

Holland Beck for the important

23:31

work that you are doing and

23:33

will continue to do. It

23:36

makes such a difference and I

23:38

know you've made us a whole lot smartyr

23:40

today listening to you. Thank

23:42

you so much, Thank you so much for having

23:44

me, and thanks for your interest in this work.

23:46

Appreciate it.

23:49

It's amazing to see how dedicated

23:52

researchers like Dr Holland

23:54

Beck are tackling some of the world's

23:56

most pressing challenges. Here

23:59

are three things things I took from that conversation.

24:03

First, while COVID has

24:05

been a global plague, it's

24:07

also brought about incredible collaboration

24:10

among scientists worldwide, and

24:13

that has resulted in tremendous

24:15

progress against the disease

24:18

in an incredibly short time. Second,

24:22

Dr Hollandback reminds us that

24:25

good science requires a diversity

24:27

of viewpoints and backgrounds. As

24:30

she says, different people bring

24:32

a different set of experiences to the

24:34

table, and that diversity

24:37

is crucial as we train the next generation

24:40

of scientists. Finally,

24:44

Dr Holland Back shows us how personally

24:46

rewarding scientific research

24:48

can be. She says that working

24:51

to solve problems like COVID makes

24:54

her feel a little

24:56

bit less helpless in the

24:58

face of what we've all ex variant.

25:02

Tune in next time to hear about our next

25:04

Featured Woman and discover

25:07

why she's one of Seneca's

25:09

one hundred Women to Hear. Seneca's

25:13

one hundred Women to Hear is a collaboration between

25:15

the Seneca Women Podcast Network and I

25:17

Heart Radio, with support from founding partner

25:19

PNG Have a Great Day,