The Discovery Of Microbes And Implications For Public Health Today, With Science Writer Thomas Levenson

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On this week's episode, Thomas Levenson, MIT professor and author of So Very Small: How Humans Discovered The Microcosmos, Defeated Germs — And May Still Lose The War Against Infectious Disease talks about what he learned in the writing of So Very Small, how cultural and political forces shape scientific progress, and what it means for drug developers, public health officials, and patients everywhere.   

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Episode Transcript

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(00:44):
Welcome back to the Business ofBiotech.
I'm your host, Ben Comer,chief Chief editor Editor at
Life Science Leader, and I'mthrilled to speak today with Tom
Levinson, a professor at MIT'sgraduate program in science
writing and the author of sevenbooks on diverse topics,
including the Science of Climate, A Musical History of Science,

(01:04):
Isaac Newton's investigativework for the Royal Mint in
London, Albert Einstein's BerlinPeriod, the Search for the
Hypothetical , Vulcan and othertopics.
He's also the recipient of aGuggenheim Fellowship and has a

(01:24):
Peabody Award to his credit forwork he did on a series for PBS.
Tom just recently published, atthe end of April, a book on the
history of germ theory calledso Very Small how Humans
Discovered the Microcosmos,Defeated Germs and May Still
Lose the War Against InfectiousDiseases.
We're going to dive into someof the themes, people and issues

(01:45):
Tom writes about in so VerySmall, because the history of
germ theory has importantimplications for public health
today, as well as thedevelopment of new antibiotics
and therapeutics.
What's past is prologue, asShakespeare wrote, and with the
shakeup happening currently atNIH, HHS and FDA, I think it's a

(02:06):
timely conversation.
Thanks so much for being here,Tom.

Thomas Levenson (02:10):
Thank you for having me.
It's great to have a chance totalk with you.

Ben Comer (02:13):
I thought we could start with the genesis of so
Very Small.
What made you want to write it?

Thomas Levenson (02:21):
Well, I kind of have to blame my wonderful
London-based editor, neil Belton, who is a formidable nonfiction
editor and currently head of animprint for Bloomsbury called
Head of Zeus, over in London,for a variety of reasons.

(02:46):
We met up for a coffee and hetold me that he was working on
this series of books that weresupposed to be very short you
know, 25,000 words or somethingon decisive moments.
You know some like singleincident that then could be, you
know, used to look at somethinglarger, and so, for example, he
had the first production ofHandel's Messiah, which opens up
all kinds of interesting doorsinto, you know, music and you

(03:09):
know the sort of socialstructure, all that kind of
stuff.
And another example he gave mewas a look at the creation of
Picasso's painting Guernica,about, you know, the Nazi
bombing of this Spanish townduring the Spanish Civil War.
That was kind of a trial runfor later blitzkrieg tactics,
and these were great books.

(03:30):
And he had, you know, a bunchof others that he had on his
list and he's a very innovativeeditor.
And he said I don't have anyscience, got to give me some
science.
And so at that time I justfinished the Newton book you had
mentioned and I was looking atsome you, I was looking at some
new stuff that also had somekinds of physics connections and

(03:52):
I said, well, there's anobvious one.
You know, when Albert Einsteingoes up the mountain at Mount
Wilson in 1930 and you come backwhere the universe has changed,
he's seen the first images thatsay the universe is expanding
and that's a complete you know,that's a real radical change in
our understanding of you know,reality on the larger scale.
I said the other thing that youknow and I said I'm not the

(04:12):
person to write this, I'm not abiology writer, you know I'm not
saying this, but it's reallybeen fascinating to me all these
years that you have the germtheory revolution in the late
19th century.
You know, depending on you,know, you can, you can sort of
put the dates where you want,but you know by convention the
date that Robert Koch one of thetwo sort of giant figures that

(04:34):
are associated with the germtheory moment in particular,
other being Louis Pasteur Kochfigures out the life cycle of
the anthrax bacillus anddemonstrates decisively that
that bacillus B, b anthracis isin fact the pathogen that brings
about a case of anthrax.
And that happens, you know,starting three days before

(04:54):
Christmas in 1876.
And he sort of finishes theexperiments before the end of
the next January, end of thenext January.
And so, like that, 1870s, 1880s,1890s, decisive moment before
disease and our understanding ofour relationship to the worlds,
of, you know, world's biology,the whole idea of the causation

(05:17):
of disease, all these kinds ofthings is one way, and
afterwards it's different, andit's different in ways that that
give human beings hugeadvantages in the millennia long
struggle with infectiousdisease.
This is a great topic.
Somebody should write this, gofind somebody to write it.
And he never did.
Series came and went, all thatwas done, and he and I would

(05:37):
meet over the years and I didtwo other books with him and
with my American editors and wewould occasionally talk about it
, american editors, and we wouldoccasionally talk about it.
And I have to say I didn't knowthat there was really a full
book there until I startedthinking well, you know, how do
you get to the moment where Koch, you know, figures out anthrax.

(05:57):
It's just taking that as thatsort of marker.

Ben Comer (06:01):
And that was a story that you were already familiar
with or already knew sort ofmarker, and that was a story
that you were already familiarwith or already knew the Koch
and anthrax discovery.

Thomas Levenson (06:10):
I knew the out, you know it's, it's.
I'm a, I'm a magpie of ascience writer and I read very
widely, and so I know a littlebit about a lot of the history
of science and you know, but Iwouldn't have called myself, you
know, deeply knowledgeable, Ifeel like I.
I know it pretty well now, butI was not more than 1870s

(06:31):
newspaper reader.
Level of knowledge up to thatpoint was obviously the
identification of microbes andspecific as the agents of
disease and specifically thateach disease was associated with

(06:54):
a single microbe.
So there was a very carefullyconstructed chain of cause and
effect and that's the greatbreakthrough that leads to all
kinds of possibilities inresponding to these infectious
diseases.
All kinds of great things thatwe'll talk about, I'm sure, in a
few minutes.
But the you know it turns, ofcourse, on identifying the fact
that microbes exist at all.

(07:15):
Right, and I was thinking allright, well, when were bacteria
discovered?
And this I actually knew, andknew pretty well because I've
spent a lot of time in the 17thcentury and spent a lot of time
in the early days of the RoyalSociety.
And basically, microbes werefirst seen in 1676 by this Dutch
draper cloth merchant namedAnthony van Leeuwenhoek.
Again, apologies to anyone whospeaks Dutch out there for my

(07:38):
butchering of that name.
I'm sure, sure, but you know,sort of like 200 years, almost

(08:00):
to the day, runs between thefirst observation of microbes,
bacteria, and the demonstrationthat they actually matter to us
in a really consequential way.

Ben Comer (08:26):
And I said that's a long time.
Why did it take so long?
And that was the question thatgot the book started.
Why did it take so long?
It made it a the 1660s.
I'm going to butcher this aswell, but Van Lowenhoek is sort
of looking at these, you know,little squigglies, as a curioso,
you know almost as a form ofparlor entertainment, you know,
and then 200 years go by beforethat connection is drawn between
these microbes and infectiousdisease.
How do you dive into that?

(08:47):
How do you?

Thomas Levenson (08:54):
get started.
I sort of feel like as myprofessor hat goes on and it's
like don't try this at home,kids, because I'm somebody who
spends a lot of time.
I like primary sources, I likereading the early philosophical
transactions of the RoyalSociety and Leuvenhoek's letters
and so forth.
All of Leuvenhoek's not all ofthem, but an enormous corpus of

(09:14):
Leuvenhoek's letters to theRoyal Society and to others are
online In English translation,parallel Dutch and English, and
you can just go read them, playaround with them, see what he
was looking at, see what he wasthinking about, see how he
expressed himself.
The you know there were.
You know there's a body ofhistory of science, work on germ

(09:37):
theory, of course, and on thediscovery of microbes, history
of biology, and so I'll bothlook at some of the you know
just to get started.
I'll start, you know, gettingsome of people I know will be
characters in the book and I'lltry and get their words and
their thoughts and their storiesas just part of in my head,
part of the sort of thinkingthrough how the storytelling in

(09:59):
the book.
The book tries to make somearguments and, I hope, some
fairly compelling and usefularguments, but it does so by
telling stories that you canthen draw meaning out of.
It's not just sort of anacademic essay.
I don't work that way.
So getting in touch with thepeople who are involved in the

(10:20):
work is really an importantfirst step, and the other first
step is to really try and seewhat the arc of the book is
where you know how this, howthis, in particular this, this
200 years of halting discoverywent from just seeing microbes
to recognizing one of theimportant things that they they

(10:42):
mean for us, mean for the earth,one of the important things
that they mean for us, mean forthe earth.
So I spend some time with someof the scholarly literature on
it.
And then the thing I do and Ido this quite early on, I do it
as I'm writing the proposal forthe book, which is about 10,000,
between 6,000 and 10,000 wordsusually.

(11:03):
So it's a fairly substantialdocument in itself I really try
and think through what the arcof the book is as a matter of
plot, what incidents areimportant to the development of
this idea, and once I've gotthose, then it becomes quite
simple.
Simple as in, the task issimple, the work may not be easy

(11:24):
.
It becomes quite simple.
You are simple as in, the taskis simple, the work may not be
easy, but you know, if you know,one thing I want to do is find
out, you know, how the 17thcentury reacted to the discovery
of microbes, and it is, as yousay, primarily as kind of a a
drawing room curiosity, muchmore than the sort of enormous
scientific breakthrough which, Ihave to say, I was talking with

(11:44):
somebody about this recentlyand it's still kind of bizarre,
I mean think, what our reactiontoday would be to have real
proof of life on other planets.
It'd be a huge deal.
In the 17th century no one hadany idea that there was this
whole realm of living creaturesyou know beyond our senses,

(12:07):
inaccessible to us with thenaked eye.
And yet there they were, theywere discovered, they could be
seen by others once Levinhugshowed them how an entire,
previously unexpected domain oflife.
How is that not a big deal?
I still don't, you know.
I don't quite you know.
The past is a different country, they do things differently
there, but that still is kind ofamazing to me.

Ben Comer (12:30):
That's one of the things that I found really
compelling about the book, wherethe way that is the way that
you stitch these stories ofindividual people making
discoveries and then trying totake them forward, sometimes
against pretty remarkablereactions or pushback from

(12:51):
society in general and even fromother scientists.
I mean, one of the themes thatI wanted to ask you about in
this book, I think, touches onthe hubris of human beings.
I mean, the cultural influenceof Christianity runs very deep
in Western culture, in the BibleGod makes humans, you know, and
his image grants them dominionover every living thing on earth

(13:15):
, which gives rise to the greatchain of being concept which you
discuss, essentially ahierarchy developed in the
Middle Ages, placing humansbelow God and angels, but above
animals, plants and minerals,and it's the idea that we're not
of nature but above and apartfrom it.

Thomas Levenson (13:37):
And so I wanted to ask you know what you might
say about that, how human hubrishas played a role in the
history of germ theory,acceptance and its practice that
these lovely, cute littlesquiggling things that Latham
Hook saw could matter to us ifyour whole cultural framework

(14:10):
says, you know, agency flowsdown, god has ultimate agency
and he grants it to it.
Whatever you know, the genderof God passes it on to us and we
, you know, as God's agents.
And in the 17th century you hadpeople, you know, who really

(14:30):
understood themselves to be insome senses God's agents, or
even, you know, mortal angels onearth.
There's some beautiful writingabout you know how this Isaac
Newton himself had this sense ofhis role as as, as you know,
directly deputized by God, insome ways very deeply held, I

(14:52):
would say.
You know, I think in, you knowWestern, in European and North
American culture, americanculture, you know the expansion
of the European world, yes, theChristian sort of framework has
enormous and lasting culturalsignificance, but the idea of
human exceptionalism is onethat's expressed in other
cultures as well.
But it's that sense that we areuniquely empowered in this

(15:19):
world.
We are big brains and opposingthumbs and we're a tool using,
and God has given us thisbeautiful created world in which
we can do things like you know,make our living through
agriculture or honey or, youknow, whatever it may be, and
and I think that made itextremely difficult to recognize
that something is diminutiveand seemingly unimportant.

(15:41):
I mean we hadn't that notknowing about them, you know,
hadn't seemed to make adifference to us up to that
point.
You know, I think it's veryhard to imagine those little
critters, you know, swimming ina drop of water, as having
agency on their own, you know,having some way to get at us.

(16:01):
And I think there are two things.
First of all, I think thathuman get at us, and I think
there are two things.
First of all, I think thathuman exceptionalism, even when
the explicitly Christian framingof it drops away, that lasts
into our own day, I mean that'sstill a very powerful, I think,
cultural impulse and you can seeit across.
You know all kinds of things,including our politics right now

(16:28):
.
I mean you mentioned changes atNIH and so forth.
I think some of the sort ofdeep you know where the license
to do that comes from for thepeople who are trying to, you
know, make these changes comesfrom.
I think that sense of you knowhuman beings as the actors and
everything else is the actedupon.
So that continues.
And I also think that you knowthe great chain of being, in
that sort of hierarchy ofcreation, is something that

(16:51):
people you know applied as anotion to all kinds of other
things, including human society.
So, you know, in European orEuropean world culture, you know
upper class white men are atthe top and everything else
flows downhill.
And that becomes a problem whenyou look at some very specific
incidents in the history of germtheory, as for example, when

(17:15):
not just the famous story inVienna but the with Ignaz
Semmelweis, but the earlierfolks who figured out that
horrible fever, childbed fever,this infection that kills women
who have just given birth, youknow there was a pretty clear

(17:36):
series of demonstrations thatthis was a problem caused in
some way by the doctors ormidwives, the medical people
attending those births, andpeople were able to document,
you know, as early as the late18th century, that this was most
likely something that wastransmitted.

(17:57):
They didn't know what it wasbeing transmitted, but the sort
of epidemiological, the diseasedetective links between a doctor
or midwife and a chain ofpatients who would suffer, all
suffer these infections wasreally clear.
You know it was established.
Well, and in response to one ofthese, oliver Wendell Holmes Sr
, not the Supreme Court Justicewho was his son, but the dad,

(18:21):
who was a poet and doctor andother things early in his career
in the 1840s, you know, saidthis and the response you know
he was a young doctor at thetime and he was not a specialist
in maternal care and the sortof leading textbook writing
OBGYN doctor of the day inPhiladelphia responded no, no,

(18:43):
no, you know, that's themaunderings of a sophomore,
couldn't be.
And because this is a quote, agentleman's hands are clean.
So the idea of a hierarchy isthere, yeah.

Ben Comer (18:55):
Yeah, just by dent of being a gentleman, yeah, and I
wanted to touch on some of theother historical misconceptions
that have functioned as a, youknow, a block or a resistance to
acceptance of the scientificresearch.
I wonder if you could explain,maybe briefly, miasmas and what
role that concept played.

Thomas Levenson (19:16):
Sure, I mean, think about, you know, an
infectious disease outbreakbefore you know, like, for
example, the incident thatstarts the book the Great Plague
of London.
So plague shows up in 1665.
There's a first, you knowthere's an index case that
probably isn't actually an indexcase, but there's an early case

(19:36):
that people refer to in a poorparish.
And then over the next coupleof months a few more cases pop
up, um.
And then over the over the nextcouple of months a few more
cases pop up and then um, thenthe disease becomes much more
widespread and the death tollsstart rising until you get um in
what was still a quite small Imean a fairly small city by
modern standards.

(19:56):
You know enormous death tolls,1 000, 2 000 people a week,
whatever um.
And you needed to explain twothings how an individual case of
the plague got started and thenhow did it spread.
And there were a number ofideas about mechanisms of

(20:22):
disease, some ideas that wouldyou know from classical
antiquity, about, you know,keeping the body in balance, the
poor humors, some more moreseemingly modern, though still
with much of the same apparatus,so-called chemical, chemical
medicine, where it was a morespecific, you know some more

(20:44):
specific substance that was inor out of balance.
So that was how the disease,you know, that was sort of what
the definition of disease was,something that caused your body
to start running awry, which isand this is important to
understanding why this idea wasable to last so long.
You know, at least as ametaphor, that's not a bad, you

(21:06):
know, way to think about adisease, right, you know?
Think about diabetes.
Your insulin metabolism doesn'twork anymore, your insulin
levels go out of balance andyou're in trouble and you treat
it by, you know, you know, with,by one way or another, bringing
those insulin levels back into,into a safe range.
Everything we know about themechanism of diabetes is

(21:30):
different from what people knowabout the plague in 1665.
But that sort of metaphoricallevel you can sort of see how
it's an effective way to frame adisease, persuasive, an
imbalance, right, yeah.
And similarly for the contagion,for how to get it from place to
place, how does it get to aperson in the first place, and
then how does it travel?
A miasma literally means badair, um, and so the idea was

(21:50):
that there is some, you know, ifyou believe it, it's that every
disease is simply god'sjudgment.
God sort of opens the fissuresof the earth and you know foul
air bearing disease, you knowbalance, you know unbalancing
stuff goes out and you know itallows for a disease to arrive

(22:11):
someplace and you know if it'sreally in that sort of sense
airborne, you can see how itwould spread.
They did in that period use theterm and have the concept of
contagion, which you know theroot means literally to touch.
So you would touch somethingthat was, you know, affected by
a disease and that touch wouldcommunicate something that could

(22:33):
then be passed on.
But by the 17th century,certainly, contagion had been
sort of loosened as a concepthad been loosened and sort of
brought into the idea thatproximity rather than actual,
necessarily sort of mechanicaltouch was necessary.
But once you have miasmas youhave a way for the disease, that
contagion, to occur and youknow keep passing from person to

(22:56):
person.
And the important thing tounderstand is that you know you
look at, you look at a diseasespreading through a city, as the
plague did through London inthat period, and you combine the
models of disease itself as anunbalancing and that the seeds

(23:18):
of disease, whatever they may bethey use terms like that, seeds
of disease could be carriedsort of invisibly on these, you
know gusts of air, or you knowair blowing it onto the person
of the.
You know somebody who's in asick room and you know carries
it with them in a breeze, blowsit to the next person.
However you want to, you know,start mapping out the individual

(23:41):
scenarios in your head.
It's not a bad description.
And so the ideas persist, inpart because you know, even if
they don't tell you really whatto do about an illness, other
than sort of attempt to bringthings into balance by, you know
, cooling people or eatingpeople or giving people beer, or
you know bloodletting orwhatever it may be.

(24:02):
These, you know some way tobring one of the bodily systems
into balance.
There's no specific mechanism,so there's no specific treatment
that's available.
But if you're just trying topaint a picture of what seems to
be happening, that does apretty good job, and that's sort
of.

(24:22):
One of the big problems forgetting to germ theory is you
have to come up with somethingthat's not just more correct but
is in some ways, you know, morepersuasive, more directly
supported, has some, you know,leads to some direct possibility
of action, and that takes along time, especially, as you
know, in some senses miasmatheory is quote true, I mean,

(24:44):
yeah, if you live on top of asewer, if you don't have, you
know, especially as you know, insome senses miasma theory is
quote true, I mean, yeah, if youlive on top of a sewer, if you
don't have, you know properhygiene and all these kinds of
things.
You know the bad smells and theyou know decaying flesh and all
this sort of stuff are signalsthat something's going on.
Miasma theory doesn't tell youwhat is going on, but you know,
it's a, it's close enough to bedifficult to dislodge.

Ben Comer (25:09):
Right, right, and it creates essentially a barrier
for someone who is making adiscovery and attempting to go
against that now commonlyaccepted wisdom.
I wonder and there were anumber of names that I had not
heard in this book, which isanother reason I really liked it
that I had not heard in thisbook, which is another reason I

(25:30):
really liked it.
I wonder if you could give anexample or two of some of the
maybe lesser sung historicalfigures who helped develop the
science behind germ theory, andyou talk about a number of
different diseases in the book,so I'll let you choose.
Well.

Thomas Levenson (25:47):
I think consistently the figure that
people are most surprised abouthearing is Cotton Mather.
We know Cotton Mather as this.
You know.
I certainly you know I livehere in the Boston area and
Cotton Mather is our.
You know hellfire and brimstonewitch burning.
You know Puritan Bible thumper.
You know Puritan Bible thumperand you know he was all those

(26:08):
things.
But he was also somebody whoapparently as a young man
actually thought about becominga doctor, was profoundly
interested in the.
You know he didn't have adisciplined mind, he was a
complete magpie, but he wasprofoundly interested in the
natural world.
He became a fellow of the RoyalSociety.
He sent them you know lots ofletters about sort of American
curiosities, some of which were,you know, clearly sort of you

(26:30):
know he was credulous about,about wild reports, but some of
it was very you know a lot ofnatural history.
He was fascinated with medicine.
He composed an entire bookcalled the Angel of Bethesda.
That was manuscript.
He left it as a manuscript whenhe died and it wasn't actually
discovered and published untilyou know the 20th century.

(26:52):
But it's a sort of anencyclopedia of everything that
he could gather about healthcare and medicine, how you would
prepare recipes for you knowthis or that and it contains
some really interesting thingsabout germ theory, in fact,
actually to me very important.
He comes into the book becausehe is one of the two great sort

(27:18):
of English speaking pioneers ofimmunization it's not true
vaccination but it's thepredecessor, it's the precursor
to modern vaccination,inoculation with smallpox.
He learned about that processfrom his enslaved servant, a man
he named Onesimus, who had beenborn in Africa and taken from

(27:40):
Africa to Boston and then giftedto Mather by some of his
parishioners.
And Onesimus had had smallpoxinoculation.
He received that in Africa andso when Mather asked him if he
had had smallpox, mather recordshis answer as yes and no,

(28:01):
didn't have it in the wild, hada reaction to the smallpox
inoculation and is now immune tothe smallpox inoculation and is
now immune.
Shortly after, you know, a fewyears after that conversation,
an Italian doctor working inConstantinople in the Ottoman
Empire reports that the you knowTurkish medicine does the same

(28:23):
thing and that was published inthe Royal Society's transactions
and Mather saw it and wrote tothe secretary of the Royal
Society's transactions.
And Mather saw it and wrote tothe secretary of the Royal
Society saying I can affirm this.
I've heard this story from myslave and from other people
who've had contact with Africa.
And the next time a smallpoxcomes to Boston I want to try it
here, which he did tosignificant success and

(28:48):
significant opposition.
I mean anti-vax sentimentstarts right at the beginning.
It's still with us but has itsroots in the reactions to these
experiments in the early 18thcentury, and so that's one of
the ways Mather gets into thestory.
The other way is this remarkable?
In this Angel from Bethesdamanuscript he writes down

(29:12):
explicitly the speculation thatthese microbes that Levenhut and
he names Levenhut, you know byname cites him.
These microbes the term wasanimicules, these little animals
, as they were known thatLevenhut has identified.
They're everywhere, they're onleaves and they could be the

(29:34):
sources of specific diseases,and we should really look at
that.
And to me that's bothfascinating.
This is in like 1720, 1721,something like this.
So, 150 years before germ theoryproper actually makes its way
into science, as it were.
And it's important to mebecause it shows that the

(29:56):
difficulty in working out germtheory wasn't simply, and
perhaps for much of this period,not mostly scientific.
It was one of finding the waysto ask the right questions and
then pursue it.
You know, mather was not anexperimentalist.
He was not a disciplined man,disciplined scientific mind, so
he wasn't the person to followthat up, but he could think it

(30:17):
right, and there was at leastone or two other people who were
thinking the same thoughts then, but they were still born
thoughts.
Nothing happened, and that, tome, is one of the things I
really want to understand in thecourse of.
You know the story I tell inthe book.

Ben Comer (30:32):
I think it's easy in 2025 to looking back at history
and seeing.
You know, the gentleman's handis always clean.
You know, miasma, we justtalked about looking backward
and saying, wow, it's incrediblethat you know these brilliant
discoverers and people who madethese forward leaps in germ

(30:57):
theory faced resistance.
You know, we couldn't be in asituation like that today.
We couldn't have those samekinds of dogmas and biases In
2025, you write in the book.
It's hard to recognize whatone's assumptions omit, all the
more so when those assumptionsare born of individuals and a

(31:17):
society's shared beliefs aboutthe interplay of the natural and
human worlds.
My question is you know they'redifficult to identify.
I think that should go withoutsaying.
But are there some existingbiases or dogmas today in
medical or scientific research,and how might we go about better

(31:40):
detecting them?

Thomas Levenson (31:44):
That's a huge question and it's tricky because
some of the issues are withscientific research and some of
them are with sort of thequestions for the larger.
You only do the science that asociety is willing to entertain
right.
We're seeing that explicitly.
There was an election inNovember.
The results of that electionwere what they were and there

(32:06):
are decisions being made aboutwhat the NIH should be doing,
what the NSF should be doing andso on, basically every federal
government science researchagency and you know you can only
do what, and that's in somesense that's the expression of
what you know a substantialchunk, you know enough of a

(32:29):
chunk of our society now toachieve political power.
That's what they think isimportant or unimportant and
that's not necessarily what ascientist, an individual
scientist or you know adiscipline as a you know
consensus or near consensusmight find important as a
consensus or near consensusmight find important.

(32:50):
So right now, for example, youhave explicitly a shifting of
NIH attention, health and HumanServices attention from
infectious diseases to so-calledchronic diseases.
That's a choice.
I think it's a wrong choice.
I think it's a terriblydangerous and scary choice.

(33:11):
But you know that tells youthat.
You know there's an assumptionthere.
There are that and again, likemost assumptions throughout the
history of all this, it's notaltogether wrong that you know
there are the, the 21st century,intensely urbanized, you know

(33:32):
very um sort of quote, mediatedin all kinds of ways, not just
media.
But you know, our food ismediated through a whole bunch
of systems and all this kind ofthing right, a more sedentary
workforce, yeah all that sort ofstuff.
so it's.
It's not wrong to say that thishas some consequences, and it
should be.
You know it's important tostudy, but you know B anthracis

(33:55):
is still out there.
Yersinia pestis, the plaguemicrobe, is still out there.
The cholera microbe is stillout there.
You know the smallpox virus isnot that's extinct in the wild,
but polio is still just outthere and could, under certain
circumstances, roar back.
Tuberculosis is very much there, killing a million people a

(34:21):
year.
Worth focusing on.
That's an unexceptional comment.
If you say chronic diseases arethe essential problem, you know
microbes get a vote right.
Yeah, you know we may wish thatinfectious disease was not a

(34:49):
potential threat, but that, in atoken, gets you on the subway,
as it were.
I think one important thing toremember is we may know more
facts.
We may have more coherent andin some ways rigorous theories
that we use to organize thosefacts than people did in the

(35:12):
past.
It's not we made we do.
We understand infectiousdisease down to the level of
molecules and individual changesin genomes that produce
different pathogenic effects,all these kinds of things, and
our predecessors did not.
But that knowledge isn't thesame as saying that we are

(35:33):
smarter than our predecessors,or that our habits of mind are
somehow cleansed and more youknow, more rigorous they're not.
You know we're not smarter thanyou know Isaac Newton and
Robert Boyle and you know allthose folks, huygens, or whoever
you want to you want to throwin.

Ben Comer (35:51):
We have the same hardware.

Thomas Levenson (35:53):
Yeah, and so you know, it would be
presumptuous of me, as you know,a popular science historian, to
say you know, these are theassumptions that people are
making in science and medicinethat are clearly going to.
You know, these are theassumptions that people are
making in science and medicinethat are clearly going to, you
know, bite us in the butt.
But I feel pretty confidentsaying that those tricky

(36:16):
assumptions exist.

Ben Comer (36:17):
Are there parallels that you see between mapping the
human genome and mapping themicrocosmos?

Thomas Levenson (36:26):
Yes, and I see them both.
As you know, it's an.
You know doing so produces thisextraordinary trove of of facts
and I think one of the thingsthat's most fascinating to me
about the Human Genome Project.
You know, I'm I'm I'm not in myfirst youth, as you can tell

(36:47):
from my hair color and all that.
I'm old enough to remember.
And, and you know, I'm not inmy first youth, as you can tell
from my hair color and all thatI'm old enough to remember.
And you know, I started work asa science writer in the 1980s
and it was a big deal tosequence a single gene and to
identify its protein.
You know you'd look for the genefor you know sickle cell trait
or the gene for Huntington's orwhatever.
And you know very intensesearch for these particular

(37:12):
sequences of DNA.
And you know a whole PhD thesiswould be a graduate student
working through one gene, oreven you know part of one gene,
because it was so laborious andso slow.
And in that context people saidoh great, we sequence.
You know, we build thetechnology, we do all this sort
of stuff and we sequence thewhole human genome and then
we'll know how to build a humanbeing and we'll understand all

(37:35):
these diseases and we'll be ableto do all this stuff.
And so they sequence the wholehuman genome and, with each
successive level of detail andprecision in our understanding
of the basic informationenvironment of molecular biology
, how DNA works in us or in aplanarium, the C elegans

(37:56):
flatworm or whoever thechimpanzee what's been striking
is how much more complex itturns out to be Our assumptions
about what kinds of knowledgeand power we will get out of
doing, say, sequencing the humangenome.
You know, as we now know I meanI was just seeing a marvelous

(38:20):
paper that suggested that thereis an important, you know, rna
mechanism for deciding which ofa couple of different proteins
sequences of DNA may produce.
That it sort of dictates whichbits of DNA get expressed and

(38:41):
you make different proteins.
And this is one of the ways youget to build something as
complex as you or me.
The ways you get to buildsomething as complex as you or
me despite the fact that we onlyhave 20 or 30,000 genes, which
was one of the first shockingand very difficult to understand
results of doing the HumanGenome Project.
How could you make us out of sofew genes, especially when

(39:02):
seemingly simpler creatures insome cases had many more genes.
What's that all about?
And I think the same is true ofthe microbial world, cataloging
the entire microbial world,especially if you include, as
modern usage does, viruses as asubset of the microbial world.
You do all that.

(39:24):
I mean there's a question ofwhat it means to catalog them,
identifying strains, doinggenomes for each of them, the
whole.
You know there are lots ofthings you can do, enormous
amounts of useful stuff to comefrom that.
At the same time, I think itwill expose us to enormously
fascinating problems that simplydoing that cataloging will not

(39:47):
be sufficient to help us figureout.

Ben Comer (39:54):
And I think a similar thing is happening with.
To get back to microbes, themicrobiome, there were a number
of drug companies who you know.
In the last 10 years, or maybe10 years ago, there was a real
effort to design drugs thattargeted the microbiome for
various conditions and I thinkpeople found out you know,
because of the clinical failuresthat that system is much more

(40:15):
complicated than we initiallyunderstood and it's still, I
think, largely a mystery.
But is that germ theory's nextfrontier, the microbiome?

Thomas Levenson (40:24):
I think, I mean , I think it's certainly it's of
interest.
I mean, one of the thingsthat's fascinating is all right,
you know you have somethinglike.
You know, you know name yourpoison the rabies virus, or you
know the cholera, you knowcholera, whatever.
And there's a sort ofrelatively simple sequence of
cause and effect.
They, you know you, getinfected with this particular

(40:46):
microbe, certain.
You know, as we didn't then,but we now know, for example,
what specific molecular eventsthe cholera microbe sets in
motion to start sloughing thelining of your intestines and
your guts and all that,dehydrating you and all these

(41:06):
terrible things.
We understand that at amechanistic level pretty well,
very well.
So that's one thing.
We have these like sort of pointsource, individual microbes
doing individual things in yourbody.
But it was, you know, as you'resaying, with this rise of sort
of microbiomic medicine, therealization that we have more

(41:28):
bacterial cells, microbial cellsin our body than we have human
cells that we live.
You know, in some ways we'rejust the tube that carry.
You know, we're the chauffeurfor all these microbes.
We just carry them around theworld, you know, and they're
doing their thing and using usfor their ends.
But they're also symbiotes, youknow, obviously you know the

(41:48):
gut microbiome is crucial toyour.
You know your digestion andyour digestive health.
If that goes awry, you get allkinds of bad things.
And when that's healthy, youdon't have ulcers, you have all
these, you know desired outcomesoccur, and this recognition
that there is this intenselycomplex ecosystem, you know this

(42:14):
whole again sort of microbialmicrocosmos within our own
bodies, within each of our ownbodies, that, when it's healthy,
is serving essential functionsfor us.
And you obviously see examplesthroughout the kingdom of life.
You know microbes that do greatthings to allow plants to fix

(42:40):
nitrogen microbes.
You know they're all kinds ofall kinds of different ways in
which, in which sort of macroscale organisms interact with
these micro scale ones in waysthat are productive for both.
So, and you know, in some senses, the diseases that result from

(43:02):
some disruption of one'smicrobiome are conditions that
may, you know, sort of require akind of germ theory-like
breakthrough to understand.
Is it the extension of germtheory specifically Will?
Well, you know germ theory wasreally built around isolating

(43:30):
individual microbes and goingthrough a series of steps to
rigorously show what theirproperties were and what their
effects were on whatever theyhave to infect.
And I don't think that simplesort of fairly straightforward
experimental protocol is goingto really be the driver of what
is, I think, a much more complex, much more multidimensional

(43:53):
systems biology problem.

Ben Comer (43:55):
Right, they're not working in isolation and you
know there's been some reallyfascinating research done on the
gut brain access withimplications for diseases like
Parkinson's and Alzheimer'sdisease.
So yeah, I mean it seems like areally difficult one to even
study.
I wanted to ask you aboutantibiotics.

(44:16):
You raised the issue ofresponsible use of antibiotics
in so Very Small, as well as theimplications of antibiotic
resistance.
What kind of policies orfunding mechanisms do you think
are needed to adequately addressthis issue?

Thomas Levenson (44:40):
First of all, I'd like to shout out to some of
the people I've talked to overthe years or stuff I've read,
who've helped me understandmicrobial resistance.
You know, microbial resistance,uh, maren McKenna's writing has
been really great and, andshe's, you know, she's an
incredibly powerful thinker andreporter on this stuff.
And, uh, you know, there arelots of others.

(45:04):
Laurie Garrett has written verywell about this stuff.
Um, you know, and, and so youknow, nothing I say is unique or
original.
You know, original to me, theseare thoughts that people have
been working out for a long time.
That said, the antibiotics as adrug that a for-profit drug

(45:25):
discovery system is going toproduce, that's a real problem,
and it's a problem for a coupleof reasons.
One is antibiotic resistancemeans that any new antibiotic
has, you know, either a finitelifespan or real constraints on
how you use it in order topreserve its effectiveness, when
you know, when resistance is soreadily developed and then, you

(45:47):
know, spread.
And the other thing is thatantibiotics, even antibiotics
that are effective, you know thegreat thing about them is they
work right.
You know, you get an earinfection, your kid gets an ear
infection, you give them a weekor two of some drops or a pill
and and they're better, andthat's all, it's there
chronically, exactly right youknow they're not statins, right,

(46:10):
right and uh.
and so the the, just the know,this is not a criticism of a
for-profit drug company, it'sjust a fact.
These are not the kinds ofcompounds that those kinds of
institutions are set up todevelop.
So, yes, that means you know.

(46:30):
Yet, that said, the economicreturn on an end of, you know,
on a successful antibiotic isenormous.
Right, all those lives saved,all those sick days you know,
eliminated, all that sort ofstuff, the benefit to society is
huge and can be counted inmoney terms and it's huge in

(46:51):
money terms is huge and can becounted in money terms and it's
huge in money terms.
Um, so these are drugs thatthat have a social, a clear
dollars and cents as well.
As you know, it's good not forhuman beings not to die, it's
good for human beings not tosuffer.
There's a, there's a moral and,and you know, just kind of like
, um, just sort of a civic valueto it.

(47:14):
But there's also, you know if weare going to, you know, be, as
the old phrase has it, homoeconomicus.
If we're going to think thatway, it makes sense on, you know
, that sort of accounting levelas well.
And if individual, you know, ifMerck or GlaxoSmithKline,
beecham or whoever it may be,isn't set up to do that, then

(47:36):
somebody else has to, and thatsomebody else has to be
essentially, uh, so a socialcommitment.
You know, we have to decide.
We're going to spend our money,our tax dollars, on it.
We're going to develop theresearch.
We're going to supportnonprofit.
Um, you know, it could begovernmental, could be
non-governmental, doesn't matter, but we need to have an
antibiotic and, more broadly,antimicrobial drug research

(48:01):
program.
That is something we, as anindividual nation, united States
, as a, you know, developedworld with the resources to do
this, that's something we needto pay for.
And we need to pay for it notjust because it's the right
thing to do, not just because itwill save lots of lives, but
because it's, you know, it'spart of creating a sustainable,

(48:22):
you know, flourishing, thrivingand economically as well as you
know, by any other measuresuccessful society.

Ben Comer (48:30):
And ideally a majority and I'm just speaking
about the US here, but ideally amajority of people would come
together and demand that taxdollars be spent to research and
develop these new antibioticsthat so far has been difficult
to generate.
I mean, maybe another option isangel investors the exceedingly

(48:55):
rich are being talked into.
Maybe, instead of investing inspace travel and investing in
the development of newantibiotics which one is more
likely to happen is what I guessI'm getting at Is it convincing
enough people or is it, youknow, convincing the rich?

Thomas Levenson (49:17):
I mean, I'm certainly not against trying to
persuade.
You know Bill Gates, whoalready is very active
philanthropically in the healthcare space, but you know Jeff
Bezos and you know whoever to toput as much money as they care,
to as much money as they asthey can, uh, into antibiotic
research and basic science.

(49:37):
You know, say, basic biological, or you know, uh, sciences,
whatever, uh, because you knowmany of these things derive.
You know the, the, the, the,the translational gap between
curiosity driven basic discoveryand developments that directly
benefit human beings.
That gap has been shrinking andyou know many of the great

(49:59):
ideas that then you know servehuman beings well, come from,
you know, rapidly emerge fromstuff that you can't predict but
are, you know, can't predictindividually, but that we know
from decades now of experience.
This, you know, sort ofcuriosity-driven basic science

(50:20):
is the seed corn for all kindsof technology development.
That sort of flows downhillfrom it.
So, yeah, absolutely, you know,get those, get those
billionaires to give back inthat way.
But I don't think that's areliable, sustainable source of

(50:47):
you know where we, what wereally need, what we really need
.
The science is not, you know,part of the problem with
billionaires or anyone is.
You know, you saw it, forexample, in Silicon Valley
people investing in sort ofmedia ventures.
They'd be really interested init, right.
And then after a while you say,okay, well, I did that, it's

(51:10):
not.
You know it's not sustaining onits own or whatever.
I'm going away and theenterprise goes away.
And you know, all of a suddenyou have a gap where that used
to be.
If you do that in science, theproblem is not just that you
know an experiment that'shappening at the moment.
The funding goes away, stops,I'm sure.

(51:32):
You know.
You know and your audienceknows you know much better than
I.
But you know really good labshave developed over time
institutional culture.
You know set of sort ofinformal knowledge.
You know something as you know,maybe as seemingly silly as you

(51:52):
know, that cell sorter overthere needs to be, you know,
encouraged in this way to do itsjob right.
And you know just how themachines work or whatever.
But there's also, you know,sort of a collective act of
thinking that goes on inproductive, interesting labs and
you pull the funding and thosepeople scatter and the machines

(52:13):
go away and the space getsreused.
It takes just to set up a goodlab to do really cutting edge
work in a lot of these nowincreasingly precise and sort of
nanoscale or microscaledisciplines.
Just the physical act ofsetting up the lab is, you know,

(52:33):
could be a year, or you know,even more in some cases, and you
know the informal knowledge ismore than that.
You know it takes a while tobuild back a team that really
knows, you know, can sort ofcommunicate in efficient and
productive ways, so relying onbillionaires who may come and go

(53:00):
, whose interest may wane when aresult doesn't happen, and so
forth, unless those billionairesare willing to endow
institutions Sort of whathappened with the Broad
Institute and some other, theWeiss Institute at Harvard and
some other, the Weiss Instituteat Harvard, places like that
they actually have endowmentsand they can sustain themselves.
People are willing to do that.
That's great.

(53:21):
But truly the scale of sciencethese days and the scale of our
societies, where US is what?
330, some million people, manytrillion dollar a year economy,
you know, if you want to make adifference on that scale you
need sort of social levelfunding and I think you need to
do so in a way that is notsubject to the, you know, each

(53:48):
change of administration's whims.
I mean the idea not just thatyou're changing the focus of NIH
or NSF, but that you'recanceling 400 grants that have
already been awarded, on whichwork is being done.
Those labs will shut down,they'll lose all that
institutional infrastructure,that capacity and the hit to US

(54:09):
science and the hit to ourability to develop new
antibiotics, develop newvaccines, to look for new ways
of, you know, addressingmicrobial issues altogether that
will be set back for years todecades and that will have not
just American impact.
It will hurt us, hurt oureconomy and so forth, but
obviously it has worldwideimpact and it has life and death
impact on a lot of people.

Ben Comer (54:30):
Right and a number of the endowments coming in from
family offices and people areoften targeted to a specific
disease.
You know they're focused oncancer or cardiology or a rare
disease, not so much.
You know large endowments forbasic science.

(54:51):
I mean the NIH, I think, doesthe vast majority of that kind
of work or has done that kind ofwork in the past.
Are there any other, I guess,potential consequences that you
could name around?
Funding cuts to the NIH?
What's happening there rightnow?

Thomas Levenson (55:10):
Well, I think you know again I don't know more
than what any of your audienceknows from careful reading of
you know the newspapers and thenperhaps you know the next two
or three levels down of morespecialized publications.
Clearly you know shutting offfunding for you know, some
scientific research or a lot ofscientific research, directly

(55:32):
affects those particularresearch programs.
Cutting off the scienceeducational pipeline, which is
one of the things that happenswhen you cut funding for
scientific research, you don'tget graduate students in, you
don't have as many graduates inplaces.
Undergraduates, universitieslose the ability to educate
undergraduates, certainlyundergraduates who need
scholarships and all that kindof stuff.

(55:53):
So you're going to have a sortof broader based skill loss.
That'll happen, that is likelyto happen.
Another thing that's going onis a lot of the just reading
this morning, before we got onthis conversation, about a bunch

(56:16):
of the sort of data collectionthat the federal government is
doing across a wide range ofdomains, from food poisoning to
weather disasters and everythingin between.

Ben Comer (56:21):
Right, yeah, disease monitoring.

Thomas Levenson (56:24):
A lot of that is going away, at least
temporarily, and that means twothings.
One is bad things can happenout there and we won't know
about it and therefore can'taddress it or learn from it.
You know, I mean, there's oneof these bad disasters is they
teach you something you know, atgreat cost.
But we won't even be able to dothat because we won't know we,

(56:45):
you know, the scientificcommunity, the research
community won't know that.
You know an event has happenedbecause this monitoring that
we've come to rely on has goneaway, that you know an event has
happened because thismonitoring that we've come to
rely on has gone away.
And I don't I mean I don't seehow you easily replace that.
I mean we just have to, youknow, I think, fight those

(57:06):
decisions.
They're ill judged.
I think you know it's one thingto say I don't want to do.
You know I don't want toresearch cancer, I want to
research obesity.
You know, look, you know, then,vice President Biden's one of
the moonshot on cancer.
That was a, that was a decisionabout what direction to go, and

(57:33):
there were, I think, a lot ofscientists who said, as as with
the war on cancer, the originalNixon war on cancer that it's a
mistake to just put all yourfocus on that singular complex
of diseases.
There's lots of other thingsthat we need to know, including
the basic science that will helpilluminate cancer and lots of
other stuff.
So you know there are choicesthat different administration
makes and you know, okay, theyget elected, they should make

(57:54):
those decisions.
But that sort of unilaterallydisarming our ability just to
find out stuff either aboutnature or about what's happening
in our society, as nature hasits way with us, that leaves us
in an extremely vulnerableposition, and I'm really I'm not

(58:18):
sure I've answered yourquestion, but I will say that
that makes me quite scared Forour audience, listeners in
leadership positions at biotechcompanies, at pharma companies.

Ben Comer (58:28):
are there any lessons , any cautionary tales, any
messages that you would hopethey might glean from so Very
Small?

Thomas Levenson (58:37):
Well, I think you know one is that you should
probably you know it's reallyhard for a startup, I know,
which is always just, you know,trying to get everything done
before the money runs out.
But there's this, you know, yougot to have a little room in
your hip pocket for somethingunexpected.
You know, I think, the some ofthe critical, there were these

(59:02):
interesting ways by people whichmay, by which people made the
inferences that finally led togerm theory.
Some was, you know, justrepeatedly identifying the
presence of a microbe in adisease without knowing what the
mechanism was.
And another was, you know, justrepeatedly identifying the
presence of a microbe in adisease without knowing what the
mechanism was.
And another was, you know,really doing a complete
reconstruction of, you know, forexample, how cholera propagates

(59:23):
through a population that wasessentially all of germ theory
except for the germ itself.
These were people, were able towork with these ideas and think
them through and they provideda foundation for real
breakthroughs to come.
So I think you know that, thatyou know saving a little bit of
budget, a little bit of time,allowing a certain number of

(59:43):
projects that that may be notquite directly on the main line
of of of your applied researchprograms is probably a useful
thing.
More broadly, I would say thatI think the phenomenon of

(01:00:08):
infectious disease is somethingwe have largely allowed
ourselves to forget aboutbecause of the extraordinary
success of vaccines against allthe common diseases of childhood
and many other diseases, andthe power of antibiotics since
the end of World War II.

Ben Comer (01:00:27):
It's a really good point and I think I'll just
quickly interject here theprimary source.
Accounts of people dying fromcholera in the book were so
shocking to me because, you know, it's something that we haven't
seen here in my lifetime in theUS and just the speed at which
they died you know people fromfrom all walks of life it was it

(01:00:51):
was really shocking in a way toread about that, how people
experienced it in real time.

Thomas Levenson (01:00:57):
Absolutely.
And I think you know the COVIDpandemic was kind of a warning
because, terrible as it was, asdisruptive as it was, as many
people around the world who diedof it it was, you know, as a
novel disease goes.
It had what roughly, you know,before the advent of the vaccine
and so forth, it had a roughly1%, I think, mortality rate,

(01:01:19):
something like that.
I mean forgive me if my memoryis playing tricks, but I think
it was in that range which isterrible, but not society,
devastating Right Right.
Society, devastating rightRight.
Imagine.

(01:01:42):
And oh, by the way, to me COVIDis one of these great, both
tragic stories of failurebecause of the, you know,
ultimately political resistanceto basic public health that led
to many more unnecessary casesand deaths, and this
extraordinary triumph of science.
I mean to go from the publicannouncement of a disease in
December to its entire genomebeing sequenced within January,

(01:02:04):
so within weeks, not months to abasic vaccine design that's
there and manufacturable by, Ithink, april and is in people's
arms a couple months after thatas a test to widespread
manufacture and distribution bythe end of the year, to less

(01:02:25):
than a year after the firstemergency disease.
I mean that is a testimony tothe extraordinary capacity of
modern molecular biology,virology, and to the, you know,
the industrial and intellectualcapacity of both the government
and, you know, the variousstartup and established pharma
firms that were involved ingetting that vaccine out.

(01:02:47):
I mean, that was a triumph.
That was a triumph.
What I worry about is the nextemergent disease may have
similar transmissibility toCOVID, may have the same global
reach, because air travel is,you know, part of our fabric now
but has a mortality rate or,you know, has you know, more

(01:03:10):
severe consequences, though youknow, long COVID and so forth is
pretty darn severe but and ahigher mortality rate.
Imagine if COVID had had, say,a 3% mortality rate instead of
one.
So you catch the disease andyou have a 1 in 33 chance of
dying.
That would be.
I think just that changedoesn't sound huge, would be

(01:03:32):
enough to be.
That would be.
I think just that changedoesn't sound huge would be
enough to be, I think, a muchmore socially disruptive.
I mean, obviously, tragically,individuals and families
involved.
But you know, imagine if youknow and COVID was, as I said,
this sort of relatively mildwarning, you know, reminder that

(01:03:58):
the microbial world, the viralworld, is still out there and
still interacts with us in waysthat we don't always love.
The viral world is still outthere and still interacts with
us in ways that we don't alwayslove, and I think one of the
things that would be reallyworth your listenership's

(01:04:19):
attention is to think hard aboutthe kinds of infectious disease
threats that people who look atthings like zoonotic diseases,
diseases that leap from animalsto people, and perhaps some of
the more conventional or morefamiliar older diseases like
measles, which is making acomeback because our vaccination

(01:04:41):
levels are dropping All thatyou know those are areas of both
fascinating scientific inquiryand possibly important
commercial.
You know work as well.

Ben Comer (01:04:52):
Absolutely Well.
We are running short on timehere, tom.
It's been a real pleasurespeaking with you.
I really appreciate you beinghere.
Tom Levinson is a professor atMIT's graduate program in
science writing and his newestbook is called so Very Small how
Humans Discovered theMicrocosmos, defeated Germs and
May Still Lose the War AgainstInfectious Diseases.

(01:05:13):
Humans discovered themicrocosmos, defeated germs and
may still lose the war againstinfectious diseases.
I'm Ben Comer and you've justlistened to the Business of
Biotech.
Find us and subscribe anywhereyou listen to podcasts and be
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LifeScienceLeadercom.
We'll see you next week andthank you for listening.

(01:05:33):
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