November 2, 2021 • 53 mins
"Mad Cow Disease" emerged in the United Kingdom in 1986. Named from the symptoms seen in cattle, it was eventually renamed more appropriately to Bovine Spongiform Encephalopathy (BSE). When humans are infected, the disease seen is variant creutzfeldt-jakob disease (vCJD).
This episode explores the story of how a prion shaped the beef and biotech industries and revealed a failure in questions and ethics. We are joined by Dr. Fiona Houston (senior researcher and veterinarian), Anne McVey (ethics advocate and mother of a victim), and Kelly Creighton (biologics manufacturing regulatory expert).
Join us to learn how scientists tackle emerging infections, why we need to ask the hard questions, and how this prion has shaped the industry.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Annie McVey (00:00):
So we swing back and forwards between economics
(00:04):
success and ethical failure. Andthat can't be that really can't
be what we want for our worldsurely. Hi, I'm Aaron Harmon.
And I'm Diane Cox Welcome toInsight out quality. both Dan
and I build and implementquality systems in the biotech
and medical device industry. Butwe often get asked, Is this
(00:24):
really necessary? That we knowif we are doing too much too
early? Or do we even need aquality system? Our goal is to
explore questions like thesethrough real life events and
experiences shared by our guestsfrom various regulated
industries. We will show you whyquality is not just about
compliance and how when it'sdone right, it can help your
product and company improvelives and make a difference.
Aaron Harmon (00:51):
In 1967, the idea of a new type of infectious
disease came about a prion. Inthe 1980s. A prion was
recognized as the cause of aninfectious disease and cheap
called scrapey. Few years later,in 1986, another new prion
disease emerged in the UK, thisone infected cattle and was
quickly nicknamed Mad CowDisease. How did this news
disease spread? What was therisk to human health at that
(01:13):
time, no one knew the UK hisChief Veterinary Officer Mr.
Reese commented, there is noevidence that the bovine disease
is transmissible to humans.
Another key government leaderDr. William Watson advise, there
was no reason at all to believethere was a risk to human
health. They were kind of right.
There was no evidence that thisnew disease could be transmitted
to humans. Other known prionslike scrapey didn't cross
(01:36):
species barriers. However, therealso wasn't evidence. It didn't
cross the species barrier andinfect humans. Here's the
timeline. In 1986, mad cowdisease was recognized. Then in
1990, a cat got infected withMad Cow Disease, presumably from
eating contaminated meat. 1995Stephen Churchville died from a
new variant of the disease,Crutchfield Jakob disease,
(01:59):
something that resembles mad cowdisease in humans. And then in
March of 1996, a decade after itwas first found. It was
determined that mad cow diseasecould and did infect humans.
Currently, 232 people have diedfrom the disease. Mad Cow
disease has shaped regulationsin animal feed and biologics.
There's a lot to discuss aboutMad Cow disease. And to help us
(02:20):
today is Dr. Fiona Houston ofthe University of Edinburgh. Dr.
Houston graduated from the RoyalSchool of Veterinary studies in
1989, and then spent four yearsworking as a veterinarian in
Canada and in the UK, right inthe midst of the Mad Cow
epidemic. In 1997. She obtainedher PhD at the Institute for
Animal Health and Compton, whereshe led studies on the
(02:41):
pathogenesis of prion diseases.
Her work led to the discoverythat mad cow disease could
transmit through blood and intoother animals like sheep. She is
now the group leader in theRoslin Institute. Welcome to the
show, Dr. Houston.
Fiona Houston (02:54):
Thank you. Good afternoon.
Aaron Harmon (02:56):
So right off, right off the bat, what does Mad
Cow Disease look like in cattle?
If you were to see a symptomaticcow? Well,
Fiona Houston (03:05):
I graduated from vet school in 1989. And I was
working in, in practice in anarea with a lot of dairy cattle
during the peak of the BSEepidemic. So we would be called
like, fairly regularly to seeanimals that farmer suspected
had BSE, and they would betypically very nervous, they
(03:27):
would react very violently tosudden noises or touch it. They
could be quite aggressive. Theyalso had very stilted movements
and tended to fall over if theyhad to turn sharply. And
sometimes they were just what wecall diner cause, which can
occur for a whole variety ofreasons, but cattle that can't
(03:50):
get up. And sometimes they werejust present like that.
Aaron Harmon (03:55):
What tipped people on that this was something new,
and it wasn't rabies, or, youknow, just some kind of normal
aging degeneration or somethinglike that?
Fiona Houston (04:05):
Well, that they'd never been cases like, quite
like this in cattle of the agegroups that were affected. So
most of the cattle, althoughthey were adults were quite
young, they were about four orfive years old. The we don't
have rabies in the UK. So thatwasn't one of the differential
diagnoses. One of the mostcommon differentials would have
(04:28):
been Listeriosis. So infectionwith listeria bacteria. The
clinical signs for that arequite distinctive. So it was
quite easy to tell thedifference between animals that
have been affected by that. Sothey went they went rarely a
whole lot of things that lookedlike this, and that didn't
respond to any treatments.
Normally, it would be if yoususpected the case, it would be
(04:49):
confirmed by a government thatand the animal will be
slaughtered and tested.
Aaron Harmon (04:54):
So you were starting out your veterinary
career into the midst of thisepidemic crisis almost. No, what
was that? like,
Fiona Houston (05:00):
Well, I suppose at the time, it was just part of
our normal routine. And I don'tthink at that stage, the link
with human disease hadn't beenestablished yet. So it was a new
disease that had just appeared.
But there were ways of dealingwith it, you know, we had to
report the cases, but then itwas very much down to the
government, feds to deal withthem. We didn't think too much,
(05:23):
I suppose about the you know, Ithink the full impact of the
disease hadn't really hadn'treally come to the fore at that
point.
Aaron Harmon (05:36):
It was that because there wasn't believed to
be in association with theability for it to infect humans,
or was it just because it was?
Yes, I frequent?
Fiona Houston (05:44):
I think so. I mean, the government line at
that time was very much the riskto humans is minimal. You know,
this is like scrapey, and sheep,which had been around for years,
you know, didn't didn't show anysigns of transmitting to humans.
So it was there was a big changeonce the new disease in humans
emerged.
Annie McVey (06:05):
In that regard, why did it take so long to believe
that it could infect humans?
Were there? Were there just noapparent associations? Or what
else might be involved?
Fiona Houston (06:16):
I think, I think it was the, like I say, it was
very much that BSE was acompletely new disease. So we
didn't really, we didn't reallyknow how to view it. So very
much relied upon the experienceof what we knew about scrapey
and sheep, to inform riskassessments associated with BSE,
(06:38):
although there were people whotook the opposite view and said,
Well, this is a new disease, andwe should be as cautious as
possible. I think there was atendency to think, well, it's,
it's similar to scrapey. And itprobably won't transmit to
humans. I mean, typically, thesediseases don't transmit very
readily between species, it'svery unusual. And BSE was very
(07:00):
unusual in that regard, becauseit transmitted to several
different species, not just tohumans, so it also transmitted
to cats, and some zoo species aswell. I think the other thing is
that these, all of thesediseases have very long
incubation period. So typically,and what I mean by that is the
period between when anindividual becomes infected, and
(07:23):
when they develop the disease isusually yours. You know, for
other infectious diseases, it'soften days or, or weeks or
months, but it's it's typicallyyears for these diseases. That's
why the association of thedisease in humans didn't appear
until 10 years after BSE hadbeen discovered and tattle. And
(07:44):
there's no way there was no wayof telling or testing to find
out that people were infectedbefore they actually develop the
the symptoms of disease.
Aaron Harmon (07:53):
So you transition from being a veterinarian to a
researcher, you know, what madeyou make that career switch? And
how did you end up down the pathof studying the SES and Mad Cow
Disease?
Fiona Houston (08:06):
Well, I wanted to, I think I wanted to do to do
something to benefit,particularly farm animal health,
I was most interested inlivestock health and disease, I
suppose I also wanted a bit moreof an intellectual challenge. So
I decided to do a PhD inimmunology in cattle. And then
when I was finishing my PhD,that was about 1997. And it was
(08:28):
just after all the publicityabout the new variant CJD, which
was caused by BSc in cattle. Soan opportunity came up then at
the Institute I was working outto get involved with and leader,
a new group that was starting tostudy BSE in sheep, actually,
because one of the big concernswas, at that point was well,
(08:52):
it's possible that sheep havealso been exposed to BSE. BSE,
in sheep, when they'reexperimentally infected, looks
very, like scrapey. Andtherefore, there was a lot of
concern that perhaps not onlycattle, but sheep might be a
source of BSE infection forhumans. So there was an
opportunity to get involved in agreat new unit, and, you know,
(09:16):
lots of funding for research inthat field to look at the
specific risks of BSE, andsheep. And that's how I got
started in this particular areaand continued, and then the
experiments themselves, becausethe disease has such a long time
course take quite a long time.
So to see them through, couldtake several years. I think the
(09:38):
longest one we had was 12 years.
Wow. From start to finish. So
Aaron Harmon (09:42):
there had to be like so many potential things. A
researcher could have gone downfor paths, and something like
this, but so many unknowns, likewas there just tons of ideas
being thrown around that werethen being prioritized and stuff
like what that looks like from aresearch front? Yeah,
Fiona Houston (09:57):
there were so many things that that weren't
known. And I suppose we were, wewere trying to understand how
the disease might betransmitted, whether it would
change over time if it wastransmitted, you know, BSE, and
sheep, for example, whether itwas transmitted from sheep,
sheep, and would change. Therewere obvious practical
questions. And I think that thatinfluenced a lot of the
(10:18):
research, both from a publichealth point of view, and from
an animal health point of view,a lot of the funding from
government was very practicallydirected at, you know,
understanding these fundamentalquestions about about
transmission and control, andwhat the risks were,
Diane Cox (10:35):
sort of help us kind of understand how this disease
presented in humans. Could youalso speak to whether it was
able to be transmitted betweenpeople? Or is it just from the
source of the contaminatedmeats?
Fiona Houston (10:50):
Yes, this is a really interesting question. And
it was a concern right from thebeginning, that this new disease
in humans would it transmit fromperson to person and the the
roots that people were concernedabout, in particular, were via
surgical instruments, becausethe prions that cause these
diseases are known to beextremely resistant to most
(11:13):
forms of decontamination. So,the normal autoclave cycles that
you would use for surgicalinstruments wouldn't be
effective at inactivating theinfectious agent. So that was a
huge area of concern, surgicaland dental instruments and the
other one of the other majorareas was blood transfusion.
(11:33):
This was something that we, westarted to research using sheep
as a kind of model for humans.
So we took sheep that wereexperimentally infected with
BSE, and then did bloodtransfusions, and showed that
actually, the disease could bequite easily transmitted by
blood transfusion. And thensubsequent to that, I think a
total of four cases in humanswere discovered that that were
(11:56):
attributed to infected bloodtransfusions. So so there is
some evidence that bloodtransfusion, it can be a route
of human to human spread. Butthe last of those cases, I
think, was, was identified in2006. And so far, there have
been no further transfusionassociated cases.
Aaron Harmon (12:16):
When you when your lab discovered that be like,
Whoa, this is a big deal. Igotta get this out. Like, how
did that? How did you processthat information? When you
discover that? Yeah, it doestransmit from blood
transfusions?
Fiona Houston (12:27):
Well, it was a big, it was a big shock, because
I remember when I was setting upthose experiments, I, I just
thought, this is going to be themost boring experiment ever.
Because, you know, we know thatthe levels of infection and
blood are really low. So itprobably going to be a
completely negative result. Andthen when the first animal
developed the disease, Iremember I had to go to my boss
(12:50):
on the director of my instituteand say, you know, this has
happened. And it was, it wasreally was a big deal. And then
that we made the decision tobecause it was, it was so I
guess I expected we publishedthat result, straight away.
Before we got any confirmation,or we got any additional cases,
not a lot of people were saying,You that You've contaminated
(13:14):
your experiment, or this can'tpossibly happen, you know, there
was a lot of pushback from thethe scientific community saying
this, you know, you can'tpublish a result on a single
animal, and you must have made amistake. But then we confirmed
it, you know, in many other inmany other animals in that
experiment, and it's beensubsequently, you know, repeated
(13:35):
by a lot of other people. So,definitely, so it was, yeah, it
was a big deal at the time,
Aaron Harmon (13:41):
when you said that people are thought of maybe
contamination, a joke and Diane,and I kind of have is whenever
something goes wrong, andthere's an investigation within
a, within a business, the reflexis to blame the person that they
had done something wrong, theymade a mistake. That's why
whatever it was didn't work.
It's kind of a human naturething, I think.
Fiona Houston (14:00):
Yeah, exactly.
And it was so unexpected to methat we checked everything, you
know, as carefully as we could.
And we knew, you know, we didn'twant to put anything out there.
If we if we weren't certain thatit was raised. So
Diane Cox (14:14):
just from pure numbers standpoint, how, how
widespread was this, back then,when it was first discovered,
and then compared to now, thepeak number of
Fiona Houston (14:25):
cases in the UK was reached in about 1992. And
there were over 35,000 confirmedcases of BSE and cattle in that
year. And since then, it's beengoing down and no, we're at the
numbers of cases are really lowand most years there are no
cases reported but every sooften, there'll be there'll be
(14:45):
another, you know, isolatedcase. We have one in Scotland in
2018. And I think that's thelatest one in the UK.
Aaron Harmon (14:54):
What stop the epidemic.
Fiona Houston (14:57):
It really is dying to the I think the country
falls on feeding meat and bonemeal to livestock. I think quite
early in the epidemic, theepidemiologists thought that it
was consistent with a foodbornesource of infection. And they
recommended removing animalprotein from ruminant diets. And
(15:17):
that seems to have been,fortunately, there doesn't seem
to have been very muchtransmission from cattle to
cattle. So removing the theinfection source in the diet has
been effective.
Aaron Harmon (15:28):
And that was Was that pretty early on that that
was introduced?
Fiona Houston (15:31):
Yes, the first ban was introduced in 1988. But
the first Ban said that youcouldn't feed meat and bone meal
to ruminant livestock to sort ofsheep and cattle. But what they
discovered was that there werestill cases occurring. And the
reason for that was crosscontamination in feed mills. So
the same feed mills wereprocessing food for pigs and
(15:54):
poultry. And for cattle andsheep, if they were using meat
and bone meal in their pig andpoultry rations, that was
enough, there was enoughcontamination in the system to
contaminate the the cattle feed.
So in 1996, they reinforced thelegislation to say that animal
protein couldn't be fed to anylivestock. And that actually
(16:14):
includes fish, I think, up untilfairly recently, at least. So
yeah, that's pretty universal.
And that's, that was extendedacross the EU, I think, after
2000.
Diane Cox (16:27):
So I know, just being in the medical device space, we
have regulations on making surethat the whereabouts from where
our components of animal origincome from need to be known and
understood. And we need to makesure that there's plenty of
testing done to be to confirmthat there's no disease within
the components and devices thatwe're assembling. I guess, just
(16:50):
from that perspective, how wouldmanufacturers be able to confirm
such a thing, what kinds oftesting needs to be done, in
order to confirm that there's nosource of contamination in the
devices or even medicalMedicinal Products,
Fiona Houston (17:06):
it's actually really difficult because it's
not easy to detect theinfectious agent, because it's
composed of protein, only thetests we have that we you know,
that you apply to say a cellline or a particular product are
not particularly sensitive. Imean, there are there are no
much more sensitiveamplification techniques that
(17:29):
you can use. But they're notreally adapted for commercial
use. They're kind of researchtools, rather than something
that you could use to routinelytest products. And I think that
that is the biggest challenge.
So if it was a virus, forexample, you would think of
maybe using PCR to detectcontamination or something like
that, or bacterial culture, butthat's just not an option with
(17:53):
with primes.
Aaron Harmon (17:57):
Do you have a sense of like, how many prions
are needed to cause aninfection? In an animal or
human?
Fiona Houston (18:03):
That's, that's an interesting? That's an
interesting question. I can'ttell you just off the top of my
head, but it's the infectiousdoses quite low. So I think in
terms of infection experimentsin cattle, you know, they've
they've used decreasing doses ofwhat they used to infect them in
(18:26):
experiments, his brainhomogenate From an infected
animal, and they can go downbelow point one of a gram, I
think it's still sometimes getinfection. Now what that means
in terms of the number ofprotein molecules, I can tell
you, it's I imagine
Aaron Harmon (18:41):
that's hard to calculate. But yeah, it's it's
quite low. Are there recentcases of variant CJD appearing
in UK? Or is this pretty muchbeen solved with measures that
we're in but again,
Fiona Houston (18:55):
it's yeah, the the numbers of cases in humans
have have come down. Since two,they I think they reached their
peak in the year 2000. Andthey've been coming down since
then. And in the last six orseven years, there's only been
maybe one or two cases. So thelast case that I'm aware of was
in 2016. But the interestingthing about that case was their
(19:18):
genetic background was differentfrom all of the previous cases.
There's evidence that the theprion protein gene itself can
affect susceptibility todisease. And all of the cases
had one particular geneticvariant up until that point, but
this person was heterozygous atthe codon that that is
(19:40):
associated with susceptibility.
So what that means is we knowthat these genetic variants can
be associated with differentincubation periods. And
therefore, there was a bit ofconcern that actually, we might
see a second wave of cases inpeople with the who are
heterozygous just because theyhad longer incubation periods
and took longer to do Butdisease, but so far, there's
(20:00):
been no additional cases.
Aaron Harmon (20:04):
So the control measures seem to have worked
pretty good. So it's, yes, likefortuitous that that was at
least started. The year afterthat the debate didn't go on too
much longer. Yes. Yeah. Onething I'm curious about, we had
the Mad Cow Disease thing, itseems to be, you know, pretty
much slowly working its way tobeing something historical. Are
(20:27):
there other things we could seeemerge that you would could
predict? Could there besomething in poultry, something
in swine?
Fiona Houston (20:34):
One of the things we just don't really understand
this is where these diseasescome from. So we don't really
know how BSE originated in thepast few years. chronic wasting
disease that affects dear hasappeared in Norway. Now, it's
that was thought to be a problemjust in North America, previous
to that, but there doesn't seemto be any connection between the
(20:55):
cases in Norway and anyintroduction from North America.
Again, we don't reallyunderstand where has that come
from three or four years ago, anew disease, a new prion disease
emerged in camels in Algeria.
And again, nobody knows wherethat came from, you know, I
think we've got to be wary thatit could, it could appear again,
not necessarily, as you expect,pigs seem to be, I mean, there
(21:18):
was a lot of concern about pigs,and there's been quite a lot of
experimentation done on them.
And they seem more resistant tobe se than a lot of other
species. So they were fed quitelarge, you know, infected with
quite large doses of BSE, anddidn't really develop the
disease, if it was given by theoral route. I think it's, some
(21:40):
species are definitely moreresistant. And sometimes we can
infect animals experimentally bydirect inoculation into the
brain. But that doesn't reallytell you whether they would
become infected in a naturalsetting.
Aaron Harmon (21:53):
Sure. Like there's a balance in the world of things
that occur and stay controlthem, we do some things we can
set that balance off. And sothe, the meat and bone meal,
feeding that back to animalscause that imbalance. And when
that happened, we had the theoutbreak, and when that then was
taken away, it stopped it.
Fiona Houston (22:13):
But one of the interesting things is that meat
and bone meal had been includedin in animal feed for quite a
long time previous to the youknow, the 1980s, maybe not at
the same scale, that one of oneof the things that was thought
at the time was there wasderegulation of rendering
processes at the beginning ofthe 1980s. So the industry was
(22:37):
quite tightly regulated up tothen and then they relaxed some
of the regulations. People didwarn at the time, well, if you
relax these regulations youmight get they weren't thinking
of prion diseases, but theythought other infectious
diseases like salmonella, and soon might might survive in animal
feed and cause diseaseoutbreaks. Although it's never
been definitively proven thatthat was theory that that was
(23:01):
very prominent in the earlystages that actually, the
changes to rendering allied theprime agent to survive in animal
feed.
Aaron Harmon (23:09):
One of the things that Dan and I really see is
there's a lot of value inregulations. And when
regulations done well, they canhelp companies or industries
prevent things from going wrong.
And that's probably why we dothis podcast. And so it's
interesting that you mentionedthat, because that kind of
supports what we're saying, andthe fact that a regulation is
kind of what helps stop this.
(23:29):
Yeah, just goes to show theimportance of them.
Diane Cox (23:31):
Yeah, there are there are obviously possibilities for
outbreaks within animals. Buthow do we know? Or have any
intuition or studies to knowwhether it's transmittable to
humans? Is it just through thesetypes of events happening? Or is
(23:52):
there a way to kind of predictthat?
Fiona Houston (23:54):
It's a really important question, because I
think, with BSE it was, youknow, it was a very special set
of circumstances where you had alarge outbreak of disease and
cattle followed several yearslater by a completely new
disease in humans. And then inmany ways, it was easy to make
the association between Okay,BSE causes this disease in
(24:15):
humans, but for other priondiseases on a smaller scale, if
someone became infected byeating say, a sheep with scrapey
and 20 years later, developed aneurological disease. It's very
hard to make that associationjust from epidemiological data
alone, especially if yoursurveillance, your disease
surveillance isn't absolutelyexcellent, which which is not,
(24:38):
it's not universally, great, youknow that you'll have the level
of surveillance that you need tomake those associations. So we
really have to rely onexperimental evidence, and that
comes down to a lot a lot oftimes to experimental infection.
So we'll try to infect primatesas being closely related to
humans, but there are also twotransgenic mouse models which
(25:02):
have been genetically altered toexpress the human prion protein,
and therefore are moresusceptible to human prions. So
we can use them as a kind ofsurrogate of, would this
particular animal prion diseasetransmit to humans. So there are
various models like that thatcan be used to assess the risk.
But at the end of the day, youkind of then need the
(25:24):
epidemiological evidence to backthat up, because as I said,
Before, you can infect theseexperimental animals. And
usually it's done by artificialroots by inoculating into the
brain. And that doesn'tnecessarily show that it could
happen in real life. So yes, Idon't know if that answers.
Yeah, yeah, it's a question.
But, but yes, and no, you know,to try and get away from the use
(25:45):
of animal models, where we'realso trying to develop in vitro
models, where, where you sortof, you have a simplified model
for prion replication, and youcan use that and it gives you
answers a lot more quickly. Theyneed these sort of models
probably need a bit morevalidation. But in future they
might be really useful forassessing those kinds of risks
(26:06):
to humans. Sure, sure.
Aaron Harmon (26:09):
If you can remember back to when you first
heard about this new disease andanimals are in cattle. Did you
ever have any inkling that thisis going to shape your career
shape the cattle industry shaperegulations?
Fiona Houston (26:21):
No, not at all.
You know, I remember firsthearing about it and seeing my
first cases when I was a vetstudent in Edinburgh. But yes, I
had no idea of the impact on meand on the whole industry as
well.
Aaron Harmon (26:33):
It's crazy how that works out. Yeah.
Diane Cox (26:36):
Fascinating.
Aaron Harmon (26:37):
Well, thank you for being on the show,
Dr.Houston.
Fiona Houston (26:39):
Very welcome.
It's been a pleasure.
Aaron Harmon (26:42):
Now we'll take a quick break to hear from one of
our sponsors.
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show.
Aaron Harmon (27:24):
I'd like to make a transition in terms here. When
this prion disease was firstidentified, it was referred to
as mad cow disease because ofthe behavior of the cattle it
infected. Its true name isBovine Spongiform
Encephalopathy, called BSE forshort. When BSE infects the
human, the disease scene isreferred to his variant
Creutzfeldt Jakob disease calledV CJD for short. Why are these
(27:47):
terms important? Becausediseases aren't just viruses,
bacteria, parasites and prions.
They affect who we are, theyshape our lives, they take from
us physically and drain usemotionally. So it's important
that we give them a properidentity, one that calls them
for what they are or not takingaway from who we are. The
youngest victim of BSC was clearMcVeigh, she died aged 15 on
January 11, of 2000. Claire wasborn on May 29 1984. If you
(28:12):
remember the timeline from thebeginning of this episode, BSC
was first identified in 1986.
Claire was two years old. Thegovernment officials at the time
insisted there was no risk tohumans, people should continue
eating beef without worry. Theycontinued to insist it couldn't
infect humans until 1996. Threeyears later, any McVeigh
(28:36):
Claire's mom noticed somethingwas wrong with her daughter. And
he witnessed the tragedy of thisdisease in her home, she
experienced loss in a way mostof us haven't, and hopefully
never do. The worst part wasthat though she trusted to
protect her and our family toldher and everyone else that BSE
couldn't infect humans, theyerred on the side of protecting
(28:56):
an economy instead of the livesof those they were supposed to
protect. This podcast coverswhen things go wrong, not to
point fingers or to blame, butan attempt to prevent things
from happening again. We'vecovered suppliers that lied
about data, vaccinecounterfeiters, managers cutting
corners to save cost, poorlydesigned drug trials by
scientist. When we fail to doour jobs, people can die as
(29:17):
Claire did. And he has her ownapproach to helping prevent this
tragedy from happening again.
She joins us here to share.
Annie McVey (29:23):
Thank you, Aaron for having me. I've spoken a lot
about Claire since she died. Andoften people want the story of
the horror of her dying and herdeath. But I understand why. But
there's more to the story thanthat. It's about all the
decisions that were made out ofmy control before she became
(29:43):
ill. And those are the ones thatpeople continue to make every
day because businesses run. Theywant to be economically viable
and successful and they makedecisions. And I understand
that. I think all the familiesunderstand that that, you know,
businesses there for profit. Butit should be more than that is
(30:05):
the ethical considerations thatsometimes get left behind in
this race to make a goodspreadsheet at the end of each
financial year that theshareholders will be happy with.
Now, we could all do that wecould all make money, if we
never looked at the consequencesof doing that. And one of the
things that I've done sinceClaire died first in anger,
(30:29):
because those first few yearswhen you're bereaved, you're
very angry, or at least I was.
And since then, I've wanted itto be more of a positive
contribution to policymaking.
And that's to remind thepoliticians who were involved in
the BSE scandal, and the oneswho are making similar decisions
(30:52):
now that every decision theymake, has a human consequence, I
write to the politicians,usually around Christmas, that's
when our emotions are usuallyfocused on family. I also
include the Muslims ingovernment and atheists in
government. And I tried totailor my letters that might
(31:15):
speak to them, to remind themthat every decision they make
has a consequence. And sometimesthat can be a fatal consequence.
And not to take them purely forfinancial gain, because that is
disastrous for any business.
Because once you take away yourcustomer, once you can be
(31:37):
blinded to that in the searchfor financial benefit, then you
almost lose your soul. Thespreadsheet is valuable, and I
understand it. But there'sanother one, there's another
part of that balance sheet, andI just ask the politicians to
(31:58):
remember that when they sit downfor their Sunday lunch, or the
Christmas lunch, remember, I'msitting down, and there's a
space across from me. And therealways will be. And as times
gone on, there's not just onespace, there's a space for her
children, because they'remissing as well. And a partner,
you need to know that is notenough, do think a decision is
(32:23):
made. Pros and cons. It's notjust black and white, there are
gray areas. And in those grayareas, people can die. The
letter goes out, some of thosepoliticians have retired now,
but new ones take their place.
And if they're the samepolitical hue, normally, they're
making the same decisions. And Ihave to say, with Coronavirus,
(32:47):
COVID-19, they appear not tohave learned very much. And
that's that. So this year, Ithink my letter might just be a
little bit more hard hitting.
And we'll see what we get fromthat. That's my contribution.
Aaron Harmon (33:00):
I really like the approach you take. There's all
these decisions to be made inthe future, right? And we want
them to be made for the rightreasons. And they're not easy to
make. But if it's always airingtowards the balance sheet,
there's a cost to that. How didyou transition to making this
approach, you have
Annie McVey (33:15):
to become realistic after a while, initially, when
Claire was ill and died. I mean,as I said previously, it was the
anger to that, that I couldn'tthink I just wanted to punish
people. And I wanted people tohear the story and to feel the
grief I felt. Then I thoughtabout well, where do I go from
(33:36):
this because I can live my lifein anger and grief. And is that
really the best memorial to mydaughter and all the other sons
and daughters. And it seemed tobe that you have to be
realistic. When I looked atbusiness, and I saw that they
made decisions sometimes which Iwould not say were ethical. I
(33:59):
wanted to know why they madethose decisions. And the
pressures they were under to dothat. Because in 2000, when the
BSE inquiry was published,Claire had already died. And all
I could see with theretrospective nature of the
inquiry was all the mistakesthey had made. All the times
(34:21):
when they they had information,which if you didn't allow
yourself the imagination to seewhere that could go. The
consequence of that you couldnever have ignore consciousness
have continued that course ofaction. But they didn't allow
themselves to see that they wereblinded. They only wanted to see
(34:42):
what they wanted to see. Andthey wanted to avoid any
disruption to the feed industryany disruption to the meat
industry, the livestockindustry, even when it passed
from one species to another.
They didn't have the imaginationto realize that we are basic
Aliy animals, if it passes fromcow to cat, why won't it pass
(35:05):
from cat to human? Not in thesense that you, you catch it,
but in the sense that it willevolve, it will mutate. And it's
having that imagination andbeing listened to, because there
were people saying those things.
They were just not welcome atthe table. Because they're like
(35:26):
the specter at the feast, theperson who brings you down by
saying, Yeah, you can, you know,you can double your profits this
year, you can really make surethis business flies, and
somebody says yes, but And sothe way to do that, for me was
to show the, you know, if you'vegot a very cold hearted CEO,
what you do is you tell him howit will impact on his profits,
(35:49):
because a couple of largelawsuits are not going to help
his profits. So you have tospeak to the person, you have to
get to them in a way that theyunderstand. And I realized, you
know, after about a year or so,after Clara died, that I wasn't
reaching the people it wasnecessary to reach, I was
(36:11):
reaching the other parents whohadn't lost children. And they
were acknowledging the pain, andthey saw the horror. But the
people who made the decisions,just dismissed me as a bereaved
mother, they didn't think I hadanything valuable to say, or any
understanding of the positionthey were in. So you have to
(36:31):
bite your tongue, try not to behypercritical, but give
constructive criticism, which isHave you thought about this?
Have you thought about that? Iwould love to see every board,
have a person who is purelythere to give the dark side,
purely there to take down theenthusiasm and say, We need to
(36:51):
think about this. The worst casescenario, what would happen,
proper open risk management, notthe sort of closed risk
management you do in thebusiness, but something which
really does make everybodyaround that table thing. So
that's what I've been trying todo. I've been trying to be a
little more calm about thingsless emotional about things, and
(37:15):
I try to hear what the otherperson is saying. And the
pressures they're under, youknow, shareholders want money.
That's what they want. Some ofthem don't think about the
ethical product. And you needthat other person that that
everyday person who doesn't haveone narrow remit, but looks at
the whole picture, really. Andif they don't, they get a letter
(37:38):
from me at Christmas. So
Aaron Harmon (37:40):
I really appreciate you, Annie. I feel
like we're totally aligned. Oh,this should go and I'm glad you
you've gone that route and dothat.
Annie McVey (37:47):
I wish I could do more because I I think it's an
important thing to do. Thanksfor sharing with us any. That's
okay. You're welcome. And thankyou for inviting me.
Aaron Harmon (37:58):
One lesson often learned in quality is that's not
the problem. But the questionsyou asked about the problem. And
he mentioned the gray areas.
These are the areas where it'seasy to steer into a mistake,
because the answers aren'tobvious. Here's how it played
out with BSE. There was a grayarea in 1987, a new disease
appeared and there was nothingknown about that specific
pathogen. Do you shut down thebeef industry? Do you risk the
(38:19):
lives of your public? Someone orsome committee needs to make a
decision? researchers like Dr.
Houston spend their lives tryingto bring answers to the table
those trying to answer thesegray area questions. I think the
challenge in gray areas isasking the question correctly.
Example. Can anyone prove thatBSE infects humans? In 1987? The
(38:40):
answer was no. No one can provethat. How might this question
and answer impact the decisionsyou make? Now let's ask it a
different way. Still a 1987? Cananyone prove that BSE does not
infect humans? And the answer isalso no, no one can show that it
is safe for people. How doesthat impact the decisions you
make? The later is the wayquality assurance folks ask
(39:02):
questions. We want to ask, do weknow it safe? Is there a way to
make it safe? We do this to helpprevent disasters? How did BSE
affect pharmaceuticals biologicsand medical devices? There is
still research ongoing and BSE.
There are still people dealingwith the impact the pathogen had
in their lives, and in biotech,we think about this pathogen and
others and ways to stop themfrom getting into our product.
(39:23):
Joining us again to discuss theimpact that BSE has had in the
medical product industry isKelly Creighton. Welcome back to
Inside Out quality Kelly.
Kelly Creighton (39:33):
So it's good to be here again, Aaron.
Aaron Harmon (39:35):
So Kelly, you've been in the pharma and biologic
space for many years. How didyou see BSE impact this area?
Kelly Creighton (39:42):
Well, obviously it has a direct impact
ultimately on the industry, asmany people probably realize
that a lot of animal derivedproducts are used during the
manufacturing processspecifically in biologics,
things such as serum or enzymesor liquid lipids. are often used
in the cell culture processesand such that are used to
(40:05):
generate biological products. Soin that instance, right, FDA
ultimately had to address thisissue with regards to ensuring
safety and quality of thoseproducts that go in and to those
manufacturing processes, as wellas not only direct products that
go into the medical andbiological processes, but other
(40:29):
things such as like gelatin,which is a very common product
that is used to make capsules,those most gelatins, at least
definitely back in the 80s andearly 90s, were directly derived
from bovine materials. So ofcourse, FDA had had to address
this, to ensure that the drugsupply and biologic supply did
(40:54):
not put people at risk forpotential BSE infection. So in
1993, FDA issued their firstposition and first regulations
that basically required that allmammalian derived proteins, so
it also included some controlsaround Oh, Vine, the swine
(41:16):
regulations came a little bitlater. But in 1993, they issued
their first guidance andregulations with regards to
where bovine derived materialscould be sourced from. So this
basically relied on the USDAlist, which listed out all the
countries for which there hadbeen either confirmed or
(41:38):
suspected BSE cases. Andbasically put those countries on
the list of prohibited countriesthat could import any type of
bovine or ruminant derivedmaterials into the US. So that
was kind of the first impactthat we saw is that FDA limited
where you could source thosetypes of materials, ultimately,
(41:59):
right? In 2000, they came backand they did a very deep review
into all of the vaccine programsthat are on the market in the
US. Vaccines are probably one ofthe biggest users of animal
derived products that go intothe process, not ultimately
ending up in the final product,but go into the process. And
(42:20):
then 2000, they found that eventhough the regulation had been
in place for seven years, theyfound several products that were
still using bovine materialsfrom basically from the USDA
less countries, which arecountries that were banned. And
people asked hell does thishappen? Like, why could that
happen? Is because Right? Thosematerials may have been made in
(42:44):
a country that it was not on thelist. Therefore, they were
imported directly from a countrythat could import bovine bribe
materials into the US. However,they actually sourced it from
countries that were on the USDless. So that is, where's that
whole supply chain managementand understanding and people
(43:05):
really figuring out, okay, we'vegot to have better controls
around this. So at that point,FDA basically asked that all
vaccine manufacturers that hadcurrently been using products
from countries derived in the USthe less to go back and remove
those materials. And this had arather large impact for some
(43:28):
companies, because this includedgoing all the way back to cell
banks, which are typically thestarting point for the process.
And it takes a lot of work to toderive and qualify cell banks.
Now, this applies only toworking cell banks, not all the
way back to the master. So FDAagreed that the master cell
(43:49):
bank, even if it was usedmaterials from USDA, less
countries, that that was farenough back in the process that
that presented a very low risk,but all working cell banks had
to be remade and derived fromwith more materials from
countries not on the USDA less.
So all immediately had a bigimpact on on those companies as
(44:09):
they had to go back and do that.
Ultimately, right, that's FDAhas gone back and done a deep
review and dive and monitoring.
And there has never been asingle case of BSE anywhere in
the world that has been linkedto a biologic or pharmaceutical
product. So overall, right? Thecontrols that have been in place
(44:32):
now since 93, have been adequateto prevent that type of
transmission. But I can tell youworking in industry and working
heavily in the biologicsindustry, the sources and
quality of raw materials that gointo the process into a biologic
process is always a majorconcern with FDA. And anytime
you're you're presenting thatinformation to FDA, you have to
(44:55):
submit a substantial questionHave you documentation around
the product to verify that it isderived from areas or regions
that no longer have BSE and thatbasically have quality
statements, very specificquality statement, that the
product is at very low risk ofcontaining either BSC or TSC
(45:20):
agents. So that is a very big,big part of the industry now.
And as the industry has evolved,we're actually starting to see
more and more companies pivotaway from the use of animal
derived products altogether intheir manufacturing, and using
either recombinant protein typeproducts to replace enzymes or,
(45:42):
or things like that, or plantderived components. So they
industry continues to try tomove away from animal derived
products, just just to continueto address that safety risk and
try to get further away from it.
Aaron Harmon (46:00):
Sure. And even on if I understand, right, so take
bovine serum, if you purchasebovine serum for use
manufacturing, it's a beingsourced from countries that
would not be having BSEoutbreaks, then it is gamma
radiated potentially, yep,filtered to levels that would
remove any potentialcontaminating bacteria. So by
time it makes it to themanufacturing floor, it has been
(46:22):
cleaned up as much as possible.
Well,
Kelly Creighton (46:24):
right as possible. And again, right, the
prion that causes BSE is verydifficult to remove sir. So even
like the gamma radiation, butdoes not necessarily prove that.
So that is why the control goesall the way back to the source
of where those cattleoriginated, because there really
is no, quote, unquote, validatedclearance process to truly make
(46:49):
sure you can get rid of theprion throughout the process. So
that is why you have to controlit all the way back to the
source. Now now, right? So back,when talking about in 2000, all
the vaccines went under review.
At that time, basically all ofEurope was was on the USB less,
right, because it originated inUK, or at least, that's where
the first cases were. Butreally, basically all of Europe
(47:11):
ultimately got indicated, eventhough like very specific
countries never had a reportedcase like Austria, but
basically, because of openborders within Europe, and
everything all of Europe got onthe list. Now that we're getting
3040 years out from the originalfinding, there are now ways for
countries that were ultimatelyon the list to come back in. And
(47:36):
so the import restrictions havedropped for a lot of countries
that were originally on thatlist. Now, again, there's there
are still countries on the list.
And you have to be aware of thatwhen you're sourcing. And you
know, it tends we tend to seethat Australia and New Zealand
tend to be still the preferredsources for at least bovine
(47:57):
derived materials, because theywere they were never implicated
in the original. So they stilltend to be kind of the preferred
and kind of the gold standardfor source when people are
looking at sourcing bovinederived materials. But there are
a lot more countries that areable to to import into the US.
But again, it goes back to thesourcing because the lack of
(48:19):
ability of a process to trulyensure that you would kill any
type of prion if it was present,that just doesn't exist. So you
have to control it back.
Aaron Harmon (48:30):
So and then, as you mentioned, to getting away
from bovine products when youcan, there's so much effort to
get out of animal products
Kelly Creighton (48:37):
it is but you know, it's funny. One of the
things we see is like I said,for a lot of specific things,
but like enzymes, people aretrying to go to recombinant
sources. And those are derivedtypically in either bacterial or
yeast systems. And then ofcourse, right grown up by
recombinant technology and thenpurified. The tricky thing is
(49:00):
there is that a lot ofrecombinant processes also use
animal derived components. So Ihave seen FDA dig into that, and
I haven't I firsthand experiencewith FDA having a safety concern
for a product because an enzymeused in the manufacturing of a
(49:23):
certain biologic was actuallyderived from recombinant
technology. And when they duginto that recombinant technology
found that process use basicallyanimal derived products. So you
see where you can get very deeplevels not having to dig and
verify your entire supply chainof whether or not animal derived
materials are actually everchance because FDA always
(49:45):
considers once you have oneplace where those agents be at
BSE or some other type ofadventitious agent. If there's
ever a chance for those types ofagents to enter into the supply
chain, it is almost impossiblefor Most processes to ever
remove them. And so they willhave, they will make you verify
(50:05):
that all of those materials, Matcurrent standards with regards
to BSE, or advantageous or viralagent qualifications. So it can
be a very tricky issue forpeople and quality to be able to
control all the way back, youknow, maybe three or four
vendors back for raw materialthat you're using in your
(50:29):
process.
Aaron Harmon (50:30):
So that's just good reason for it. And so
you're right, no, yeah.
Kelly Creighton (50:35):
Right now, it's it's a legitimate concern from
the FDA. And I said, the systemsnow are, are well enough develop
that it's typically not thatonerous, or burdensome now to
make those links, all thosechains. But I can tell you even
going back to early 2000s, thatwasn't necessarily an easy task.
(50:58):
And also right, a lot ofproducts, biologic products and
getting developed late 90s,early 2000s. Those products,
especially like the master cell,banks, and potential you in the
working cell banks were derivedprior to 1993. So before there
ever was regulations, and sothat is where a lot of people
(51:19):
had gotten caught up. But again,right now we're getting far
enough away, that theregulations are basically just
everybody understands. Andthat's just part of part of the
industry. And there really isless concern or risk and being
able to trace your raw materialsall the way back to source at
this point.
(51:40):
I hope for those that arelistening to this episode that
are not working in the biotechspace, like we do hear this and
say, Well, they do quite a bitof effort to make sure our
products are safe. Becausethat's exactly why we do that.
That's what the FDA wants. Andthat's what we're trying to
accomplish. Exactly. Yeah. Imean, and like I said, the
industry has always been fullybehind these regulations. It's
(52:03):
not like people have pushed backor companies have been pushed
back and thought this wasoverkill, or that it was not
required. Everybody has alwayssupported them because they
understand at the end of theday, patient safety is always
the key and Paramount thing withregards to products. And nobody
wants to put patients are underduress because of some issue
(52:27):
like this. Yeah. Well, thank youfor your insights, Kelly, for
joining us. Of course, I'm happyto do
Aaron Harmon (52:32):
and stay tuned for the next episode of insight
quality.
We hope you enjoyed thisepisode. This is brought to you
thanks to South Dakota biotechAssociation. If you have a story
you'd like us to explore andshare, let us know by visiting
www. SD bio.org. Also, if youlive in the Sioux Falls area,
check out QUIBIT A local QualityAssurance Professionals Network.
(52:54):
You can find out more aboutQUIBIT by clicking on the link
on our website too. Thanks forlistening
So we swing back and forwards between economics
(00:04):
success and ethical failure. Andthat can't be that really can't
be what we want for our worldsurely. Hi, I'm Aaron Harmon.
And I'm Diane Cox Welcome toInsight out quality. both Dan
and I build and implementquality systems in the biotech
and medical device industry. Butwe often get asked, Is this
(00:24):
really necessary? That we knowif we are doing too much too
early? Or do we even need aquality system? Our goal is to
explore questions like thesethrough real life events and
experiences shared by our guestsfrom various regulated
industries. We will show you whyquality is not just about
compliance and how when it'sdone right, it can help your
product and company improvelives and make a difference.
Aaron Harmon (00:51):
In 1967, the idea of a new type of infectious
disease came about a prion. Inthe 1980s. A prion was
recognized as the cause of aninfectious disease and cheap
called scrapey. Few years later,in 1986, another new prion
disease emerged in the UK, thisone infected cattle and was
quickly nicknamed Mad CowDisease. How did this news
disease spread? What was therisk to human health at that
(01:13):
time, no one knew the UK hisChief Veterinary Officer Mr.
Reese commented, there is noevidence that the bovine disease
is transmissible to humans.
Another key government leaderDr. William Watson advise, there
was no reason at all to believethere was a risk to human
health. They were kind of right.
There was no evidence that thisnew disease could be transmitted
to humans. Other known prionslike scrapey didn't cross
(01:36):
species barriers. However, therealso wasn't evidence. It didn't
cross the species barrier andinfect humans. Here's the
timeline. In 1986, mad cowdisease was recognized. Then in
1990, a cat got infected withMad Cow Disease, presumably from
eating contaminated meat. 1995Stephen Churchville died from a
new variant of the disease,Crutchfield Jakob disease,
(01:59):
something that resembles mad cowdisease in humans. And then in
March of 1996, a decade after itwas first found. It was
determined that mad cow diseasecould and did infect humans.
Currently, 232 people have diedfrom the disease. Mad Cow
disease has shaped regulationsin animal feed and biologics.
There's a lot to discuss aboutMad Cow disease. And to help us
(02:20):
today is Dr. Fiona Houston ofthe University of Edinburgh. Dr.
Houston graduated from the RoyalSchool of Veterinary studies in
1989, and then spent four yearsworking as a veterinarian in
Canada and in the UK, right inthe midst of the Mad Cow
epidemic. In 1997. She obtainedher PhD at the Institute for
Animal Health and Compton, whereshe led studies on the
(02:41):
pathogenesis of prion diseases.
Her work led to the discoverythat mad cow disease could
transmit through blood and intoother animals like sheep. She is
now the group leader in theRoslin Institute. Welcome to the
show, Dr. Houston.
Fiona Houston (02:54):
Thank you. Good afternoon.
Aaron Harmon (02:56):
So right off, right off the bat, what does Mad
Cow Disease look like in cattle?
If you were to see a symptomaticcow? Well,
Fiona Houston (03:05):
I graduated from vet school in 1989. And I was
working in, in practice in anarea with a lot of dairy cattle
during the peak of the BSEepidemic. So we would be called
like, fairly regularly to seeanimals that farmer suspected
had BSE, and they would betypically very nervous, they
(03:27):
would react very violently tosudden noises or touch it. They
could be quite aggressive. Theyalso had very stilted movements
and tended to fall over if theyhad to turn sharply. And
sometimes they were just what wecall diner cause, which can
occur for a whole variety ofreasons, but cattle that can't
(03:50):
get up. And sometimes they werejust present like that.
Aaron Harmon (03:55):
What tipped people on that this was something new,
and it wasn't rabies, or, youknow, just some kind of normal
aging degeneration or somethinglike that?
Fiona Houston (04:05):
Well, that they'd never been cases like, quite
like this in cattle of the agegroups that were affected. So
most of the cattle, althoughthey were adults were quite
young, they were about four orfive years old. The we don't
have rabies in the UK. So thatwasn't one of the differential
diagnoses. One of the mostcommon differentials would have
(04:28):
been Listeriosis. So infectionwith listeria bacteria. The
clinical signs for that arequite distinctive. So it was
quite easy to tell thedifference between animals that
have been affected by that. Sothey went they went rarely a
whole lot of things that lookedlike this, and that didn't
respond to any treatments.
Normally, it would be if yoususpected the case, it would be
(04:49):
confirmed by a government thatand the animal will be
slaughtered and tested.
Aaron Harmon (04:54):
So you were starting out your veterinary
career into the midst of thisepidemic crisis almost. No, what
was that? like,
Fiona Houston (05:00):
Well, I suppose at the time, it was just part of
our normal routine. And I don'tthink at that stage, the link
with human disease hadn't beenestablished yet. So it was a new
disease that had just appeared.
But there were ways of dealingwith it, you know, we had to
report the cases, but then itwas very much down to the
government, feds to deal withthem. We didn't think too much,
(05:23):
I suppose about the you know, Ithink the full impact of the
disease hadn't really hadn'treally come to the fore at that
point.
Aaron Harmon (05:36):
It was that because there wasn't believed to
be in association with theability for it to infect humans,
or was it just because it was?
Yes, I frequent?
Fiona Houston (05:44):
I think so. I mean, the government line at
that time was very much the riskto humans is minimal. You know,
this is like scrapey, and sheep,which had been around for years,
you know, didn't didn't show anysigns of transmitting to humans.
So it was there was a big changeonce the new disease in humans
emerged.
Annie McVey (06:05):
In that regard, why did it take so long to believe
that it could infect humans?
Were there? Were there just noapparent associations? Or what
else might be involved?
Fiona Houston (06:16):
I think, I think it was the, like I say, it was
very much that BSE was acompletely new disease. So we
didn't really, we didn't reallyknow how to view it. So very
much relied upon the experienceof what we knew about scrapey
and sheep, to inform riskassessments associated with BSE,
(06:38):
although there were people whotook the opposite view and said,
Well, this is a new disease, andwe should be as cautious as
possible. I think there was atendency to think, well, it's,
it's similar to scrapey. And itprobably won't transmit to
humans. I mean, typically, thesediseases don't transmit very
readily between species, it'svery unusual. And BSE was very
(07:00):
unusual in that regard, becauseit transmitted to several
different species, not just tohumans, so it also transmitted
to cats, and some zoo species aswell. I think the other thing is
that these, all of thesediseases have very long
incubation period. So typically,and what I mean by that is the
period between when anindividual becomes infected, and
(07:23):
when they develop the disease isusually yours. You know, for
other infectious diseases, it'soften days or, or weeks or
months, but it's it's typicallyyears for these diseases. That's
why the association of thedisease in humans didn't appear
until 10 years after BSE hadbeen discovered and tattle. And
(07:44):
there's no way there was no wayof telling or testing to find
out that people were infectedbefore they actually develop the
the symptoms of disease.
Aaron Harmon (07:53):
So you transition from being a veterinarian to a
researcher, you know, what madeyou make that career switch? And
how did you end up down the pathof studying the SES and Mad Cow
Disease?
Fiona Houston (08:06):
Well, I wanted to, I think I wanted to do to do
something to benefit,particularly farm animal health,
I was most interested inlivestock health and disease, I
suppose I also wanted a bit moreof an intellectual challenge. So
I decided to do a PhD inimmunology in cattle. And then
when I was finishing my PhD,that was about 1997. And it was
(08:28):
just after all the publicityabout the new variant CJD, which
was caused by BSc in cattle. Soan opportunity came up then at
the Institute I was working outto get involved with and leader,
a new group that was starting tostudy BSE in sheep, actually,
because one of the big concernswas, at that point was well,
(08:52):
it's possible that sheep havealso been exposed to BSE. BSE,
in sheep, when they'reexperimentally infected, looks
very, like scrapey. Andtherefore, there was a lot of
concern that perhaps not onlycattle, but sheep might be a
source of BSE infection forhumans. So there was an
opportunity to get involved in agreat new unit, and, you know,
(09:16):
lots of funding for research inthat field to look at the
specific risks of BSE, andsheep. And that's how I got
started in this particular areaand continued, and then the
experiments themselves, becausethe disease has such a long time
course take quite a long time.
So to see them through, couldtake several years. I think the
(09:38):
longest one we had was 12 years.
Wow. From start to finish. So
Aaron Harmon (09:42):
there had to be like so many potential things. A
researcher could have gone downfor paths, and something like
this, but so many unknowns, likewas there just tons of ideas
being thrown around that werethen being prioritized and stuff
like what that looks like from aresearch front? Yeah,
Fiona Houston (09:57):
there were so many things that that weren't
known. And I suppose we were, wewere trying to understand how
the disease might betransmitted, whether it would
change over time if it wastransmitted, you know, BSE, and
sheep, for example, whether itwas transmitted from sheep,
sheep, and would change. Therewere obvious practical
questions. And I think that thatinfluenced a lot of the
(10:18):
research, both from a publichealth point of view, and from
an animal health point of view,a lot of the funding from
government was very practicallydirected at, you know,
understanding these fundamentalquestions about about
transmission and control, andwhat the risks were,
Diane Cox (10:35):
sort of help us kind of understand how this disease
presented in humans. Could youalso speak to whether it was
able to be transmitted betweenpeople? Or is it just from the
source of the contaminatedmeats?
Fiona Houston (10:50):
Yes, this is a really interesting question. And
it was a concern right from thebeginning, that this new disease
in humans would it transmit fromperson to person and the the
roots that people were concernedabout, in particular, were via
surgical instruments, becausethe prions that cause these
diseases are known to beextremely resistant to most
(11:13):
forms of decontamination. So,the normal autoclave cycles that
you would use for surgicalinstruments wouldn't be
effective at inactivating theinfectious agent. So that was a
huge area of concern, surgicaland dental instruments and the
other one of the other majorareas was blood transfusion.
(11:33):
This was something that we, westarted to research using sheep
as a kind of model for humans.
So we took sheep that wereexperimentally infected with
BSE, and then did bloodtransfusions, and showed that
actually, the disease could bequite easily transmitted by
blood transfusion. And thensubsequent to that, I think a
total of four cases in humanswere discovered that that were
(11:56):
attributed to infected bloodtransfusions. So so there is
some evidence that bloodtransfusion, it can be a route
of human to human spread. Butthe last of those cases, I
think, was, was identified in2006. And so far, there have
been no further transfusionassociated cases.
Aaron Harmon (12:16):
When you when your lab discovered that be like,
Whoa, this is a big deal. Igotta get this out. Like, how
did that? How did you processthat information? When you
discover that? Yeah, it doestransmit from blood
transfusions?
Fiona Houston (12:27):
Well, it was a big, it was a big shock, because
I remember when I was setting upthose experiments, I, I just
thought, this is going to be themost boring experiment ever.
Because, you know, we know thatthe levels of infection and
blood are really low. So itprobably going to be a
completely negative result. Andthen when the first animal
developed the disease, Iremember I had to go to my boss
(12:50):
on the director of my instituteand say, you know, this has
happened. And it was, it wasreally was a big deal. And then
that we made the decision tobecause it was, it was so I
guess I expected we publishedthat result, straight away.
Before we got any confirmation,or we got any additional cases,
not a lot of people were saying,You that You've contaminated
(13:14):
your experiment, or this can'tpossibly happen, you know, there
was a lot of pushback from thethe scientific community saying
this, you know, you can'tpublish a result on a single
animal, and you must have made amistake. But then we confirmed
it, you know, in many other inmany other animals in that
experiment, and it's beensubsequently, you know, repeated
(13:35):
by a lot of other people. So,definitely, so it was, yeah, it
was a big deal at the time,
Aaron Harmon (13:41):
when you said that people are thought of maybe
contamination, a joke and Diane,and I kind of have is whenever
something goes wrong, andthere's an investigation within
a, within a business, the reflexis to blame the person that they
had done something wrong, theymade a mistake. That's why
whatever it was didn't work.
It's kind of a human naturething, I think.
Fiona Houston (14:00):
Yeah, exactly.
And it was so unexpected to methat we checked everything, you
know, as carefully as we could.
And we knew, you know, we didn'twant to put anything out there.
If we if we weren't certain thatit was raised. So
Diane Cox (14:14):
just from pure numbers standpoint, how, how
widespread was this, back then,when it was first discovered,
and then compared to now, thepeak number of
Fiona Houston (14:25):
cases in the UK was reached in about 1992. And
there were over 35,000 confirmedcases of BSE and cattle in that
year. And since then, it's beengoing down and no, we're at the
numbers of cases are really lowand most years there are no
cases reported but every sooften, there'll be there'll be
(14:45):
another, you know, isolatedcase. We have one in Scotland in
2018. And I think that's thelatest one in the UK.
Aaron Harmon (14:54):
What stop the epidemic.
Fiona Houston (14:57):
It really is dying to the I think the country
falls on feeding meat and bonemeal to livestock. I think quite
early in the epidemic, theepidemiologists thought that it
was consistent with a foodbornesource of infection. And they
recommended removing animalprotein from ruminant diets. And
(15:17):
that seems to have been,fortunately, there doesn't seem
to have been very muchtransmission from cattle to
cattle. So removing the theinfection source in the diet has
been effective.
Aaron Harmon (15:28):
And that was Was that pretty early on that that
was introduced?
Fiona Houston (15:31):
Yes, the first ban was introduced in 1988. But
the first Ban said that youcouldn't feed meat and bone meal
to ruminant livestock to sort ofsheep and cattle. But what they
discovered was that there werestill cases occurring. And the
reason for that was crosscontamination in feed mills. So
the same feed mills wereprocessing food for pigs and
(15:54):
poultry. And for cattle andsheep, if they were using meat
and bone meal in their pig andpoultry rations, that was
enough, there was enoughcontamination in the system to
contaminate the the cattle feed.
So in 1996, they reinforced thelegislation to say that animal
protein couldn't be fed to anylivestock. And that actually
(16:14):
includes fish, I think, up untilfairly recently, at least. So
yeah, that's pretty universal.
And that's, that was extendedacross the EU, I think, after
2000.
Diane Cox (16:27):
So I know, just being in the medical device space, we
have regulations on making surethat the whereabouts from where
our components of animal origincome from need to be known and
understood. And we need to makesure that there's plenty of
testing done to be to confirmthat there's no disease within
the components and devices thatwe're assembling. I guess, just
(16:50):
from that perspective, how wouldmanufacturers be able to confirm
such a thing, what kinds oftesting needs to be done, in
order to confirm that there's nosource of contamination in the
devices or even medicalMedicinal Products,
Fiona Houston (17:06):
it's actually really difficult because it's
not easy to detect theinfectious agent, because it's
composed of protein, only thetests we have that we you know,
that you apply to say a cellline or a particular product are
not particularly sensitive. Imean, there are there are no
much more sensitiveamplification techniques that
(17:29):
you can use. But they're notreally adapted for commercial
use. They're kind of researchtools, rather than something
that you could use to routinelytest products. And I think that
that is the biggest challenge.
So if it was a virus, forexample, you would think of
maybe using PCR to detectcontamination or something like
that, or bacterial culture, butthat's just not an option with
(17:53):
with primes.
Aaron Harmon (17:57):
Do you have a sense of like, how many prions
are needed to cause aninfection? In an animal or
human?
Fiona Houston (18:03):
That's, that's an interesting? That's an
interesting question. I can'ttell you just off the top of my
head, but it's the infectiousdoses quite low. So I think in
terms of infection experimentsin cattle, you know, they've
they've used decreasing doses ofwhat they used to infect them in
(18:26):
experiments, his brainhomogenate From an infected
animal, and they can go downbelow point one of a gram, I
think it's still sometimes getinfection. Now what that means
in terms of the number ofprotein molecules, I can tell
you, it's I imagine
Aaron Harmon (18:41):
that's hard to calculate. But yeah, it's it's
quite low. Are there recentcases of variant CJD appearing
in UK? Or is this pretty muchbeen solved with measures that
we're in but again,
Fiona Houston (18:55):
it's yeah, the the numbers of cases in humans
have have come down. Since two,they I think they reached their
peak in the year 2000. Andthey've been coming down since
then. And in the last six orseven years, there's only been
maybe one or two cases. So thelast case that I'm aware of was
in 2016. But the interestingthing about that case was their
(19:18):
genetic background was differentfrom all of the previous cases.
There's evidence that the theprion protein gene itself can
affect susceptibility todisease. And all of the cases
had one particular geneticvariant up until that point, but
this person was heterozygous atthe codon that that is
(19:40):
associated with susceptibility.
So what that means is we knowthat these genetic variants can
be associated with differentincubation periods. And
therefore, there was a bit ofconcern that actually, we might
see a second wave of cases inpeople with the who are
heterozygous just because theyhad longer incubation periods
and took longer to do Butdisease, but so far, there's
(20:00):
been no additional cases.
Aaron Harmon (20:04):
So the control measures seem to have worked
pretty good. So it's, yes, likefortuitous that that was at
least started. The year afterthat the debate didn't go on too
much longer. Yes. Yeah. Onething I'm curious about, we had
the Mad Cow Disease thing, itseems to be, you know, pretty
much slowly working its way tobeing something historical. Are
(20:27):
there other things we could seeemerge that you would could
predict? Could there besomething in poultry, something
in swine?
Fiona Houston (20:34):
One of the things we just don't really understand
this is where these diseasescome from. So we don't really
know how BSE originated in thepast few years. chronic wasting
disease that affects dear hasappeared in Norway. Now, it's
that was thought to be a problemjust in North America, previous
to that, but there doesn't seemto be any connection between the
(20:55):
cases in Norway and anyintroduction from North America.
Again, we don't reallyunderstand where has that come
from three or four years ago, anew disease, a new prion disease
emerged in camels in Algeria.
And again, nobody knows wherethat came from, you know, I
think we've got to be wary thatit could, it could appear again,
not necessarily, as you expect,pigs seem to be, I mean, there
(21:18):
was a lot of concern about pigs,and there's been quite a lot of
experimentation done on them.
And they seem more resistant tobe se than a lot of other
species. So they were fed quitelarge, you know, infected with
quite large doses of BSE, anddidn't really develop the
disease, if it was given by theoral route. I think it's, some
(21:40):
species are definitely moreresistant. And sometimes we can
infect animals experimentally bydirect inoculation into the
brain. But that doesn't reallytell you whether they would
become infected in a naturalsetting.
Aaron Harmon (21:53):
Sure. Like there's a balance in the world of things
that occur and stay controlthem, we do some things we can
set that balance off. And sothe, the meat and bone meal,
feeding that back to animalscause that imbalance. And when
that happened, we had the theoutbreak, and when that then was
taken away, it stopped it.
Fiona Houston (22:13):
But one of the interesting things is that meat
and bone meal had been includedin in animal feed for quite a
long time previous to the youknow, the 1980s, maybe not at
the same scale, that one of oneof the things that was thought
at the time was there wasderegulation of rendering
processes at the beginning ofthe 1980s. So the industry was
(22:37):
quite tightly regulated up tothen and then they relaxed some
of the regulations. People didwarn at the time, well, if you
relax these regulations youmight get they weren't thinking
of prion diseases, but theythought other infectious
diseases like salmonella, and soon might might survive in animal
feed and cause diseaseoutbreaks. Although it's never
been definitively proven thatthat was theory that that was
(23:01):
very prominent in the earlystages that actually, the
changes to rendering allied theprime agent to survive in animal
feed.
Aaron Harmon (23:09):
One of the things that Dan and I really see is
there's a lot of value inregulations. And when
regulations done well, they canhelp companies or industries
prevent things from going wrong.
And that's probably why we dothis podcast. And so it's
interesting that you mentionedthat, because that kind of
supports what we're saying, andthe fact that a regulation is
kind of what helps stop this.
(23:29):
Yeah, just goes to show theimportance of them.
Diane Cox (23:31):
Yeah, there are there are obviously possibilities for
outbreaks within animals. Buthow do we know? Or have any
intuition or studies to knowwhether it's transmittable to
humans? Is it just through thesetypes of events happening? Or is
(23:52):
there a way to kind of predictthat?
Fiona Houston (23:54):
It's a really important question, because I
think, with BSE it was, youknow, it was a very special set
of circumstances where you had alarge outbreak of disease and
cattle followed several yearslater by a completely new
disease in humans. And then inmany ways, it was easy to make
the association between Okay,BSE causes this disease in
(24:15):
humans, but for other priondiseases on a smaller scale, if
someone became infected byeating say, a sheep with scrapey
and 20 years later, developed aneurological disease. It's very
hard to make that associationjust from epidemiological data
alone, especially if yoursurveillance, your disease
surveillance isn't absolutelyexcellent, which which is not,
(24:38):
it's not universally, great, youknow that you'll have the level
of surveillance that you need tomake those associations. So we
really have to rely onexperimental evidence, and that
comes down to a lot a lot oftimes to experimental infection.
So we'll try to infect primatesas being closely related to
humans, but there are also twotransgenic mouse models which
(25:02):
have been genetically altered toexpress the human prion protein,
and therefore are moresusceptible to human prions. So
we can use them as a kind ofsurrogate of, would this
particular animal prion diseasetransmit to humans. So there are
various models like that thatcan be used to assess the risk.
But at the end of the day, youkind of then need the
(25:24):
epidemiological evidence to backthat up, because as I said,
Before, you can infect theseexperimental animals. And
usually it's done by artificialroots by inoculating into the
brain. And that doesn'tnecessarily show that it could
happen in real life. So yes, Idon't know if that answers.
Yeah, yeah, it's a question.
But, but yes, and no, you know,to try and get away from the use
(25:45):
of animal models, where we'realso trying to develop in vitro
models, where, where you sortof, you have a simplified model
for prion replication, and youcan use that and it gives you
answers a lot more quickly. Theyneed these sort of models
probably need a bit morevalidation. But in future they
might be really useful forassessing those kinds of risks
(26:06):
to humans. Sure, sure.
Aaron Harmon (26:09):
If you can remember back to when you first
heard about this new disease andanimals are in cattle. Did you
ever have any inkling that thisis going to shape your career
shape the cattle industry shaperegulations?
Fiona Houston (26:21):
No, not at all.
You know, I remember firsthearing about it and seeing my
first cases when I was a vetstudent in Edinburgh. But yes, I
had no idea of the impact on meand on the whole industry as
well.
Aaron Harmon (26:33):
It's crazy how that works out. Yeah.
Diane Cox (26:36):
Fascinating.
Aaron Harmon (26:37):
Well, thank you for being on the show,
Dr.Houston.
Fiona Houston (26:39):
Very welcome.
It's been a pleasure.
Aaron Harmon (26:42):
Now we'll take a quick break to hear from one of
our sponsors.
Joni Ekstrum (26:45):
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(27:07):
here to inform, to connect, andto advocate for our critical
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hear from you. Find us at wwwthat SD bio.org. Now back to the
show.
Aaron Harmon (27:24):
I'd like to make a transition in terms here. When
this prion disease was firstidentified, it was referred to
as mad cow disease because ofthe behavior of the cattle it
infected. Its true name isBovine Spongiform
Encephalopathy, called BSE forshort. When BSE infects the
human, the disease scene isreferred to his variant
Creutzfeldt Jakob disease calledV CJD for short. Why are these
(27:47):
terms important? Becausediseases aren't just viruses,
bacteria, parasites and prions.
They affect who we are, theyshape our lives, they take from
us physically and drain usemotionally. So it's important
that we give them a properidentity, one that calls them
for what they are or not takingaway from who we are. The
youngest victim of BSC was clearMcVeigh, she died aged 15 on
January 11, of 2000. Claire wasborn on May 29 1984. If you
(28:12):
remember the timeline from thebeginning of this episode, BSC
was first identified in 1986.
Claire was two years old. Thegovernment officials at the time
insisted there was no risk tohumans, people should continue
eating beef without worry. Theycontinued to insist it couldn't
infect humans until 1996. Threeyears later, any McVeigh
(28:36):
Claire's mom noticed somethingwas wrong with her daughter. And
he witnessed the tragedy of thisdisease in her home, she
experienced loss in a way mostof us haven't, and hopefully
never do. The worst part wasthat though she trusted to
protect her and our family toldher and everyone else that BSE
couldn't infect humans, theyerred on the side of protecting
(28:56):
an economy instead of the livesof those they were supposed to
protect. This podcast coverswhen things go wrong, not to
point fingers or to blame, butan attempt to prevent things
from happening again. We'vecovered suppliers that lied
about data, vaccinecounterfeiters, managers cutting
corners to save cost, poorlydesigned drug trials by
scientist. When we fail to doour jobs, people can die as
(29:17):
Claire did. And he has her ownapproach to helping prevent this
tragedy from happening again.
She joins us here to share.
Annie McVey (29:23):
Thank you, Aaron for having me. I've spoken a lot
about Claire since she died. Andoften people want the story of
the horror of her dying and herdeath. But I understand why. But
there's more to the story thanthat. It's about all the
decisions that were made out ofmy control before she became
(29:43):
ill. And those are the ones thatpeople continue to make every
day because businesses run. Theywant to be economically viable
and successful and they makedecisions. And I understand
that. I think all the familiesunderstand that that, you know,
businesses there for profit. Butit should be more than that is
(30:05):
the ethical considerations thatsometimes get left behind in
this race to make a goodspreadsheet at the end of each
financial year that theshareholders will be happy with.
Now, we could all do that wecould all make money, if we
never looked at the consequencesof doing that. And one of the
things that I've done sinceClaire died first in anger,
(30:29):
because those first few yearswhen you're bereaved, you're
very angry, or at least I was.
And since then, I've wanted itto be more of a positive
contribution to policymaking.
And that's to remind thepoliticians who were involved in
the BSE scandal, and the oneswho are making similar decisions
(30:52):
now that every decision theymake, has a human consequence, I
write to the politicians,usually around Christmas, that's
when our emotions are usuallyfocused on family. I also
include the Muslims ingovernment and atheists in
government. And I tried totailor my letters that might
(31:15):
speak to them, to remind themthat every decision they make
has a consequence. And sometimesthat can be a fatal consequence.
And not to take them purely forfinancial gain, because that is
disastrous for any business.
Because once you take away yourcustomer, once you can be
(31:37):
blinded to that in the searchfor financial benefit, then you
almost lose your soul. Thespreadsheet is valuable, and I
understand it. But there'sanother one, there's another
part of that balance sheet, andI just ask the politicians to
(31:58):
remember that when they sit downfor their Sunday lunch, or the
Christmas lunch, remember, I'msitting down, and there's a
space across from me. And therealways will be. And as times
gone on, there's not just onespace, there's a space for her
children, because they'remissing as well. And a partner,
you need to know that is notenough, do think a decision is
(32:23):
made. Pros and cons. It's notjust black and white, there are
gray areas. And in those grayareas, people can die. The
letter goes out, some of thosepoliticians have retired now,
but new ones take their place.
And if they're the samepolitical hue, normally, they're
making the same decisions. And Ihave to say, with Coronavirus,
(32:47):
COVID-19, they appear not tohave learned very much. And
that's that. So this year, Ithink my letter might just be a
little bit more hard hitting.
And we'll see what we get fromthat. That's my contribution.
Aaron Harmon (33:00):
I really like the approach you take. There's all
these decisions to be made inthe future, right? And we want
them to be made for the rightreasons. And they're not easy to
make. But if it's always airingtowards the balance sheet,
there's a cost to that. How didyou transition to making this
approach, you have
Annie McVey (33:15):
to become realistic after a while, initially, when
Claire was ill and died. I mean,as I said previously, it was the
anger to that, that I couldn'tthink I just wanted to punish
people. And I wanted people tohear the story and to feel the
grief I felt. Then I thoughtabout well, where do I go from
(33:36):
this because I can live my lifein anger and grief. And is that
really the best memorial to mydaughter and all the other sons
and daughters. And it seemed tobe that you have to be
realistic. When I looked atbusiness, and I saw that they
made decisions sometimes which Iwould not say were ethical. I
(33:59):
wanted to know why they madethose decisions. And the
pressures they were under to dothat. Because in 2000, when the
BSE inquiry was published,Claire had already died. And all
I could see with theretrospective nature of the
inquiry was all the mistakesthey had made. All the times
(34:21):
when they they had information,which if you didn't allow
yourself the imagination to seewhere that could go. The
consequence of that you couldnever have ignore consciousness
have continued that course ofaction. But they didn't allow
themselves to see that they wereblinded. They only wanted to see
(34:42):
what they wanted to see. Andthey wanted to avoid any
disruption to the feed industryany disruption to the meat
industry, the livestockindustry, even when it passed
from one species to another.
They didn't have the imaginationto realize that we are basic
Aliy animals, if it passes fromcow to cat, why won't it pass
(35:05):
from cat to human? Not in thesense that you, you catch it,
but in the sense that it willevolve, it will mutate. And it's
having that imagination andbeing listened to, because there
were people saying those things.
They were just not welcome atthe table. Because they're like
(35:26):
the specter at the feast, theperson who brings you down by
saying, Yeah, you can, you know,you can double your profits this
year, you can really make surethis business flies, and
somebody says yes, but And sothe way to do that, for me was
to show the, you know, if you'vegot a very cold hearted CEO,
what you do is you tell him howit will impact on his profits,
(35:49):
because a couple of largelawsuits are not going to help
his profits. So you have tospeak to the person, you have to
get to them in a way that theyunderstand. And I realized, you
know, after about a year or so,after Clara died, that I wasn't
reaching the people it wasnecessary to reach, I was
(36:11):
reaching the other parents whohadn't lost children. And they
were acknowledging the pain, andthey saw the horror. But the
people who made the decisions,just dismissed me as a bereaved
mother, they didn't think I hadanything valuable to say, or any
understanding of the positionthey were in. So you have to
(36:31):
bite your tongue, try not to behypercritical, but give
constructive criticism, which isHave you thought about this?
Have you thought about that? Iwould love to see every board,
have a person who is purelythere to give the dark side,
purely there to take down theenthusiasm and say, We need to
(36:51):
think about this. The worst casescenario, what would happen,
proper open risk management, notthe sort of closed risk
management you do in thebusiness, but something which
really does make everybodyaround that table thing. So
that's what I've been trying todo. I've been trying to be a
little more calm about thingsless emotional about things, and
(37:15):
I try to hear what the otherperson is saying. And the
pressures they're under, youknow, shareholders want money.
That's what they want. Some ofthem don't think about the
ethical product. And you needthat other person that that
everyday person who doesn't haveone narrow remit, but looks at
the whole picture, really. Andif they don't, they get a letter
(37:38):
from me at Christmas. So
Aaron Harmon (37:40):
I really appreciate you, Annie. I feel
like we're totally aligned. Oh,this should go and I'm glad you
you've gone that route and dothat.
Annie McVey (37:47):
I wish I could do more because I I think it's an
important thing to do. Thanksfor sharing with us any. That's
okay. You're welcome. And thankyou for inviting me.
Aaron Harmon (37:58):
One lesson often learned in quality is that's not
the problem. But the questionsyou asked about the problem. And
he mentioned the gray areas.
These are the areas where it'seasy to steer into a mistake,
because the answers aren'tobvious. Here's how it played
out with BSE. There was a grayarea in 1987, a new disease
appeared and there was nothingknown about that specific
pathogen. Do you shut down thebeef industry? Do you risk the
(38:19):
lives of your public? Someone orsome committee needs to make a
decision? researchers like Dr.
Houston spend their lives tryingto bring answers to the table
those trying to answer thesegray area questions. I think the
challenge in gray areas isasking the question correctly.
Example. Can anyone prove thatBSE infects humans? In 1987? The
(38:40):
answer was no. No one can provethat. How might this question
and answer impact the decisionsyou make? Now let's ask it a
different way. Still a 1987? Cananyone prove that BSE does not
infect humans? And the answer isalso no, no one can show that it
is safe for people. How doesthat impact the decisions you
make? The later is the wayquality assurance folks ask
(39:02):
questions. We want to ask, do weknow it safe? Is there a way to
make it safe? We do this to helpprevent disasters? How did BSE
affect pharmaceuticals biologicsand medical devices? There is
still research ongoing and BSE.
There are still people dealingwith the impact the pathogen had
in their lives, and in biotech,we think about this pathogen and
others and ways to stop themfrom getting into our product.
(39:23):
Joining us again to discuss theimpact that BSE has had in the
medical product industry isKelly Creighton. Welcome back to
Inside Out quality Kelly.
Kelly Creighton (39:33):
So it's good to be here again, Aaron.
Aaron Harmon (39:35):
So Kelly, you've been in the pharma and biologic
space for many years. How didyou see BSE impact this area?
Kelly Creighton (39:42):
Well, obviously it has a direct impact
ultimately on the industry, asmany people probably realize
that a lot of animal derivedproducts are used during the
manufacturing processspecifically in biologics,
things such as serum or enzymesor liquid lipids. are often used
in the cell culture processesand such that are used to
(40:05):
generate biological products. Soin that instance, right, FDA
ultimately had to address thisissue with regards to ensuring
safety and quality of thoseproducts that go in and to those
manufacturing processes, as wellas not only direct products that
go into the medical andbiological processes, but other
(40:29):
things such as like gelatin,which is a very common product
that is used to make capsules,those most gelatins, at least
definitely back in the 80s andearly 90s, were directly derived
from bovine materials. So ofcourse, FDA had had to address
this, to ensure that the drugsupply and biologic supply did
(40:54):
not put people at risk forpotential BSE infection. So in
1993, FDA issued their firstposition and first regulations
that basically required that allmammalian derived proteins, so
it also included some controlsaround Oh, Vine, the swine
(41:16):
regulations came a little bitlater. But in 1993, they issued
their first guidance andregulations with regards to
where bovine derived materialscould be sourced from. So this
basically relied on the USDAlist, which listed out all the
countries for which there hadbeen either confirmed or
(41:38):
suspected BSE cases. Andbasically put those countries on
the list of prohibited countriesthat could import any type of
bovine or ruminant derivedmaterials into the US. So that
was kind of the first impactthat we saw is that FDA limited
where you could source thosetypes of materials, ultimately,
(41:59):
right? In 2000, they came backand they did a very deep review
into all of the vaccine programsthat are on the market in the
US. Vaccines are probably one ofthe biggest users of animal
derived products that go intothe process, not ultimately
ending up in the final product,but go into the process. And
(42:20):
then 2000, they found that eventhough the regulation had been
in place for seven years, theyfound several products that were
still using bovine materialsfrom basically from the USDA
less countries, which arecountries that were banned. And
people asked hell does thishappen? Like, why could that
happen? Is because Right? Thosematerials may have been made in
(42:44):
a country that it was not on thelist. Therefore, they were
imported directly from a countrythat could import bovine bribe
materials into the US. However,they actually sourced it from
countries that were on the USDless. So that is, where's that
whole supply chain managementand understanding and people
(43:05):
really figuring out, okay, we'vegot to have better controls
around this. So at that point,FDA basically asked that all
vaccine manufacturers that hadcurrently been using products
from countries derived in the USthe less to go back and remove
those materials. And this had arather large impact for some
(43:28):
companies, because this includedgoing all the way back to cell
banks, which are typically thestarting point for the process.
And it takes a lot of work to toderive and qualify cell banks.
Now, this applies only toworking cell banks, not all the
way back to the master. So FDAagreed that the master cell
(43:49):
bank, even if it was usedmaterials from USDA, less
countries, that that was farenough back in the process that
that presented a very low risk,but all working cell banks had
to be remade and derived fromwith more materials from
countries not on the USDA less.
So all immediately had a bigimpact on on those companies as
(44:09):
they had to go back and do that.
Ultimately, right, that's FDAhas gone back and done a deep
review and dive and monitoring.
And there has never been asingle case of BSE anywhere in
the world that has been linkedto a biologic or pharmaceutical
product. So overall, right? Thecontrols that have been in place
(44:32):
now since 93, have been adequateto prevent that type of
transmission. But I can tell youworking in industry and working
heavily in the biologicsindustry, the sources and
quality of raw materials that gointo the process into a biologic
process is always a majorconcern with FDA. And anytime
you're you're presenting thatinformation to FDA, you have to
(44:55):
submit a substantial questionHave you documentation around
the product to verify that it isderived from areas or regions
that no longer have BSE and thatbasically have quality
statements, very specificquality statement, that the
product is at very low risk ofcontaining either BSC or TSC
(45:20):
agents. So that is a very big,big part of the industry now.
And as the industry has evolved,we're actually starting to see
more and more companies pivotaway from the use of animal
derived products altogether intheir manufacturing, and using
either recombinant protein typeproducts to replace enzymes or,
(45:42):
or things like that, or plantderived components. So they
industry continues to try tomove away from animal derived
products, just just to continueto address that safety risk and
try to get further away from it.
Aaron Harmon (46:00):
Sure. And even on if I understand, right, so take
bovine serum, if you purchasebovine serum for use
manufacturing, it's a beingsourced from countries that
would not be having BSEoutbreaks, then it is gamma
radiated potentially, yep,filtered to levels that would
remove any potentialcontaminating bacteria. So by
time it makes it to themanufacturing floor, it has been
(46:22):
cleaned up as much as possible.
Well,
Kelly Creighton (46:24):
right as possible. And again, right, the
prion that causes BSE is verydifficult to remove sir. So even
like the gamma radiation, butdoes not necessarily prove that.
So that is why the control goesall the way back to the source
of where those cattleoriginated, because there really
is no, quote, unquote, validatedclearance process to truly make
(46:49):
sure you can get rid of theprion throughout the process. So
that is why you have to controlit all the way back to the
source. Now now, right? So back,when talking about in 2000, all
the vaccines went under review.
At that time, basically all ofEurope was was on the USB less,
right, because it originated inUK, or at least, that's where
the first cases were. Butreally, basically all of Europe
(47:11):
ultimately got indicated, eventhough like very specific
countries never had a reportedcase like Austria, but
basically, because of openborders within Europe, and
everything all of Europe got onthe list. Now that we're getting
3040 years out from the originalfinding, there are now ways for
countries that were ultimatelyon the list to come back in. And
(47:36):
so the import restrictions havedropped for a lot of countries
that were originally on thatlist. Now, again, there's there
are still countries on the list.
And you have to be aware of thatwhen you're sourcing. And you
know, it tends we tend to seethat Australia and New Zealand
tend to be still the preferredsources for at least bovine
(47:57):
derived materials, because theywere they were never implicated
in the original. So they stilltend to be kind of the preferred
and kind of the gold standardfor source when people are
looking at sourcing bovinederived materials. But there are
a lot more countries that areable to to import into the US.
But again, it goes back to thesourcing because the lack of
(48:19):
ability of a process to trulyensure that you would kill any
type of prion if it was present,that just doesn't exist. So you
have to control it back.
Aaron Harmon (48:30):
So and then, as you mentioned, to getting away
from bovine products when youcan, there's so much effort to
get out of animal products
Kelly Creighton (48:37):
it is but you know, it's funny. One of the
things we see is like I said,for a lot of specific things,
but like enzymes, people aretrying to go to recombinant
sources. And those are derivedtypically in either bacterial or
yeast systems. And then ofcourse, right grown up by
recombinant technology and thenpurified. The tricky thing is
(49:00):
there is that a lot ofrecombinant processes also use
animal derived components. So Ihave seen FDA dig into that, and
I haven't I firsthand experiencewith FDA having a safety concern
for a product because an enzymeused in the manufacturing of a
(49:23):
certain biologic was actuallyderived from recombinant
technology. And when they duginto that recombinant technology
found that process use basicallyanimal derived products. So you
see where you can get very deeplevels not having to dig and
verify your entire supply chainof whether or not animal derived
materials are actually everchance because FDA always
(49:45):
considers once you have oneplace where those agents be at
BSE or some other type ofadventitious agent. If there's
ever a chance for those types ofagents to enter into the supply
chain, it is almost impossiblefor Most processes to ever
remove them. And so they willhave, they will make you verify
(50:05):
that all of those materials, Matcurrent standards with regards
to BSE, or advantageous or viralagent qualifications. So it can
be a very tricky issue forpeople and quality to be able to
control all the way back, youknow, maybe three or four
vendors back for raw materialthat you're using in your
(50:29):
process.
Aaron Harmon (50:30):
So that's just good reason for it. And so
you're right, no, yeah.
Kelly Creighton (50:35):
Right now, it's it's a legitimate concern from
the FDA. And I said, the systemsnow are, are well enough develop
that it's typically not thatonerous, or burdensome now to
make those links, all thosechains. But I can tell you even
going back to early 2000s, thatwasn't necessarily an easy task.
(50:58):
And also right, a lot ofproducts, biologic products and
getting developed late 90s,early 2000s. Those products,
especially like the master cell,banks, and potential you in the
working cell banks were derivedprior to 1993. So before there
ever was regulations, and sothat is where a lot of people
(51:19):
had gotten caught up. But again,right now we're getting far
enough away, that theregulations are basically just
everybody understands. Andthat's just part of part of the
industry. And there really isless concern or risk and being
able to trace your raw materialsall the way back to source at
this point.
(51:40):
I hope for those that arelistening to this episode that
are not working in the biotechspace, like we do hear this and
say, Well, they do quite a bitof effort to make sure our
products are safe. Becausethat's exactly why we do that.
That's what the FDA wants. Andthat's what we're trying to
accomplish. Exactly. Yeah. Imean, and like I said, the
industry has always been fullybehind these regulations. It's
(52:03):
not like people have pushed backor companies have been pushed
back and thought this wasoverkill, or that it was not
required. Everybody has alwayssupported them because they
understand at the end of theday, patient safety is always
the key and Paramount thing withregards to products. And nobody
wants to put patients are underduress because of some issue
(52:27):
like this. Yeah. Well, thank youfor your insights, Kelly, for
joining us. Of course, I'm happyto do
Aaron Harmon (52:32):
and stay tuned for the next episode of insight
quality.
We hope you enjoyed thisepisode. This is brought to you
thanks to South Dakota biotechAssociation. If you have a story
you'd like us to explore andshare, let us know by visiting
www. SD bio.org. Also, if youlive in the Sioux Falls area,
check out QUIBIT A local QualityAssurance Professionals Network.
(52:54):
You can find out more aboutQUIBIT by clicking on the link
on our website too. Thanks forlistening
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