Personalized Public Health in Africa: Balancing Disease, Privacy and Ancestry

Transcript

• 00:04OK. We're going to go ahead
• 00:05and get started tonight.
• 00:06Thank you so much for coming for joining us.
• 00:09And for those who are dialed in on Zoom,
• 00:12just a couple of quick housekeeping issues.
• 00:14We have a terrific schedule for 2024,
• 00:18which is available on the website.
• 00:20Just if you just go biomedical ethics
• 00:22at Yale, you'll find yourself,
• 00:23you'll find pretty easily to get to
• 00:26the program for Biomedical Ethics and
• 00:27you'll see the schedule for the spring,
• 00:29which looks very exciting.
• 00:30But we wanted to finish off
• 00:322023 on a high note.
• 00:34And so I want to tell you a bit
• 00:36about our speaker for this evening.
• 00:37I just not too long ago met Steve
• 00:40Schiff and was so excited to be
• 00:42able to kind of bring him into our
• 00:44bioethics community because, you know,
• 00:46it's Yale's a pretty big place and there's
• 00:47people around here that if you don't know.
• 00:49And I see that, I see some student
• 00:52bioethics leaders among us as well.
• 00:54So when you're sometimes looking for members
• 00:55of the faculty to address to students,
• 00:57it's good to get to know these guys too.
• 01:00Steve Schiff is a professor and
• 01:01vice chair for Global Health in the
• 01:03Department of Neurosurgery here at Yale.
• 01:05But I should say he is professor,
• 01:06but as of relatively recently,
• 01:09he's also in fact the Harvey and Kate
• 01:11Cushing Professor of Neurosurgery,
• 01:13which is which is as they say, not nothing.
• 01:16So this is a very important
• 01:18endowed professorship.
• 01:18So congratulations for that,
• 01:21Steve.
• 01:21He's a pediatric neurosurgeon with
• 01:23interest in neural engineering,
• 01:25Sustainable health engineering
• 01:26and global health.
• 01:27He received his NIH Directors
• 01:29Pioneer and Transformative Awards
• 01:31in 2015 and 2018 respectively.
• 01:34The support enabled him to lead the
• 01:37recent discovery and characterization
• 01:39of neonatal panabesiliosis,
• 01:41a new disease syndrome that is an
• 01:44important 'cause of infant sepsis
• 01:47and hydrocephalus in East Africa.
• 01:49And that's a conversation you
• 01:50and I need to have afterwards,
• 01:52maybe at dinner because I need
• 01:53to learn more about that.
• 01:54I don't know nothing about that.
• 01:55He's taught neuro ethics at the
• 01:57undergraduate and graduate levels
• 01:58and is deeply involved in the
• 02:00ethics of ancestral genomics in
• 02:02predictive personalized public health,
• 02:04which is what we're going to
• 02:05hear about tonight,
• 02:05specifically those efforts in Africa.
• 02:09Steve is largely a product
• 02:11of Duke University.
• 02:12He received his MD,
• 02:13did his surgery residency there,
• 02:15his neurosurgery residency there,
• 02:17also received a PhD in Physiology
• 02:19and then went to CHOP to train
• 02:22in pediatric neurosurgery.
• 02:23So Professor Steve Schiff,
• 02:25we're so pleased you're here
• 02:26and please join me in welcoming
• 02:33most of you guys kind of know the drill.
• 02:34So just to remind you and
• 02:35those who are on the call,
• 02:36there'll be a talk of about 45 minutes,
• 02:38maybe a little bit longer,
• 02:39a little bit less depending
• 02:41on how our speakers feeling.
• 02:42And then I'll moderate AQ and A.
• 02:43So you'll have a chance after the talk.
• 02:45And those who are on Zoom,
• 02:47put your questions in through
• 02:48the Q&A function on Zoom,
• 02:49if you would, and then we'll have
• 02:51a conversation that'll take us.
• 02:53And but at at 6:30 at the latest,
• 02:56I will close it up.
• 02:57So you don't have to wonder how
• 02:59long you're going to be or even
• 03:00if the questions are really good
• 03:01and the conversation's great.
• 03:02We will stop.
• 03:03So we'll be done at 6:30 to set you
• 03:05free to go and and read, you know,
• 03:07some neurosurgery texts all night or
• 03:09whatever it is that you're inclined to do.
• 03:11And for now,
• 03:12I turn it over to Steve.
• 03:13Thank you,
• 03:14Sir.
• 03:14Thanks
• 03:14very much, Martin. And thanks to everyone
• 03:17for the invitation. Here, let me.
• 03:25Yeah.
• 03:42So
• 03:44let me tell you a bit of a story
• 03:48about some of the work that
• 03:51we've been doing and is
• 03:56people is this the microphone? I need?
• 04:00No. Do I this thing?
• 04:23That's right.
• 04:37All right,
• 04:41that should work.
• 04:43So I put an outline together of of
• 04:46what I'll talk to you about tonight
• 04:48and let's start off with the global
• 04:53code of conduct for research in
• 04:57Research resource Poor Settings.
• 05:01And this is a a consensus document
• 05:05that's been worked on for several
• 05:08years and it really highlights
• 05:11some of the differences that ought
• 05:14to be considered in working in
• 05:18countries in the developing world.
• 05:21This year they changed the title
• 05:23of this to say the Trust Code.
• 05:26I think that's an effort to
• 05:29hide what it's about.
• 05:32Perhaps the European Parliament has
• 05:35adopted this as its ethics for how
• 05:39European countries ought to conduct
• 05:42research in the developing world.
• 05:45And there are two overarching principles.
• 05:50The 1st is that you need to develop
• 05:54local community partnerships.
• 05:57There's been a long history of what
• 06:01has been termed colonial science.
• 06:06We sit in institutions like this,
• 06:08dream of wonderful research projects
• 06:11and go out and find a place where
• 06:14we can carry those projects out,
• 06:16publish papers and there's
• 06:18very little benefit locally.
• 06:20So that's the second major principle is
• 06:24that there should be local social value.
• 06:28So and that's a key difference to what we
• 06:33typically do in an institution like Yale.
• 06:36We have people here with very
• 06:39successful academic careers.
• 06:41We value the creation of knowledge,
• 06:45but we have with all due respect we
• 06:48have people here who work on number
• 06:50theory that if you did that in rural
• 06:54Africa it might be very interesting,
• 06:57but it doesn't improve the lives or the
• 07:00health of the people that you've worked with.
• 07:03And so curiosity based research
• 07:06is something that these global
• 07:10codes advocate that we don't
• 07:12do in vulnerable populations.
• 07:14So you add general and local value to to
• 07:21how we value science and interesting delay.
• 07:25So I am a pediatric neurosurgeon
• 07:29and the most common indication for
• 07:31operating on the brain of children
• 07:34is that they have hydrocephalus,
• 07:36they build up fluid and we do a
• 07:39variety of different kinds of surgery
• 07:42to relieve pressure on the brain.
• 07:45The vast,
• 07:47vast majority of children with hydrocephalus
• 07:51are in the the developing world.
• 07:54The largest concentration of cases is in
• 07:58sub-Saharan Africa and the most common
• 08:01cause is infection earlier in life.
• 08:05This is very different from what we see
• 08:07in the US or in Europe or Australia,
• 08:09where hydrocephalus following infections
• 08:11is not at all of that common anymore.
• 08:21I have had the privilege for the last
• 08:2416 years of collaborating with this
• 08:27small hospital in eastern Uganda.
• 08:30It's the Cure Children's Hospital.
• 08:33It specializes in neurological
• 08:36surgery of children.
• 08:39Forty of their hydrocephalus cases,
• 08:41which are their most common need for surgery,
• 08:4540% are post infectious,
• 08:4830% are children born with spina bifida,
• 08:52an open spine.
• 08:53They're also called neural tube defects,
• 08:56so we have to surgically close their back.
• 08:59Once their back is closed,
• 09:012/3 or more of those children will
• 09:04need to be treated for hydrocephalus.
• 09:08And this delay here,
• 09:12malnutrition is a pervasive
• 09:15comorbidity for all of these patients.
• 09:18And I'll get back to that a
• 09:21little later on in the talk.
• 09:27Most infectious hydrocephalus,
• 09:29as I'm describing here,
• 09:32if you were to look inside the brain,
• 09:35you'd see with a scope,
• 09:38very small pustules lining what
• 09:41is called the appendimal surface
• 09:44of the ventricles in the brain.
• 09:47These are small postules
• 09:48with space in between them.
• 09:50They don't tend to become confluent.
• 09:53There's a variety of things that that
• 09:56we could discuss regarding that,
• 09:58but we see this throughout
• 10:01sub-Saharan Africa.
• 10:02The sites that are able to
• 10:04operate on these children.
• 10:06The first thing I saw walking
• 10:08into an operating room in Vietnam,
• 10:10it's exactly the same phenomenon.
• 10:13We're not in Haiti right now,
• 10:15but my colleagues who've operated
• 10:18in Haiti have seen again the
• 10:20same type of syndrome.
• 10:22It's completely uncharacterized.
• 10:24And so much of the work that
• 10:29I'll show you today is an effort
• 10:32to learn more about this.
• 10:35So I visit this site in 2007 and
• 10:42in discussing with their physicians,
• 10:45I I was very impressed with just how hard
• 10:48it is to do technical neurosurgery in a
• 10:52setting where the resources are not ample.
• 10:55And I actually asked the medical director,
• 11:00all right, what's the most
• 11:03important problem you can't solve?
• 11:07And he answered nicely.
• 11:08It was Ben Wharf,
• 11:09who's now on faculty at Harvard.
• 11:12And And Ben said, well, why don't you
• 11:15figure out what makes these kids sick?
• 11:16And I thought, how hard can that be?
• 11:222023 was really the year that
• 11:24we finished up with the first
• 11:26set of answers to that question.
• 11:29So it's been a long journey
• 11:31here and we finally needed the
• 11:36resources of some major NIH support.
• 11:40It's interesting to me,
• 11:42it was a struggle to get NIH to
• 11:45support this because it was felt
• 11:47to have no feedback and impact on
• 11:50the health of the United States.
• 11:53Excuse me, Steve.
• 11:56Yeah, definitely the weak link of the crowd.
• 11:57So forgive you that I would move that and
• 12:00I have to phone up.
• 12:02Yeah, I can also just talk into this thing.
• 12:06I just hate standing.
• 12:09Is that any better? It is.
• 12:12All right, So we got enough resources
• 12:15from NIH to put together the kind
• 12:18of study you'd want to do here.
• 12:20Get very high quality samples,
• 12:22put together a cryogenic
• 12:25infrastructure that didn't exist.
• 12:27Get thousands of samples safely shipped,
• 12:30frozen to the US And in recent
• 12:36years I'll describe what we found.
• 12:38But in the last several years
• 12:41there've been multiple cases that
• 12:43are identical seen in the US.
• 12:49What do you do when you
• 12:51can't grow an Organism?
• 12:53This is a brutally difficult set of strains
• 12:57to get to grow in culture it turned out.
• 13:02And so if you don't know what causes
• 13:05infection, you can do several things.
• 13:07All bacteria have genes that
• 13:09are only present in bacteria,
• 13:11so you can amplify them and sequence them.
• 13:14And we have large databases so you
• 13:17can tell what at least the genus is,
• 13:19if not the species of of
• 13:23an uncultured bacteria.
• 13:24We confirm this with things
• 13:28like RNA seq or PCR targeted to
• 13:31what we think we've found.
• 13:34RNAC is also critical.
• 13:35There's no one gene in viruses,
• 13:38so if you want to look for an
• 13:41unbiased survey for what viruses
• 13:43might be infecting someone or
• 13:45what parasites might be present,
• 13:47then you're dealing with RNAC.
• 13:55By 2020, we'd teamed up with people
• 14:00both from Penn State and from Columbia
• 14:04University and found that there was only one
• 14:07Organism that dominated these infections.
• 14:10It's an unusual one.
• 14:11It was a painy bacillus, which is
• 14:14Greek or Latin for almost a bacillus.
• 14:19It formed a highly neurotropic and
• 14:22destructive infection of the brain.
• 14:24You can see one of the images of one of the
• 14:27infant brains here with calcified abscesses.
• 14:31We did manage to get some
• 14:34of these strains to grow,
• 14:37figuring out when these children got
• 14:41sick and how this apparent infection
• 14:44might have related to previous disease.
• 14:49We just finally put together and reported
• 14:543 simultaneous linked case control trials.
• 14:58This is 1400 patients,
• 15:01thousands of samples,
• 15:03over 2500 qPCR reactions to confirm what we
• 15:10had found and this involved a maternal trial.
• 15:15Many infants catch infections during
• 15:18the process of birth or there
• 15:22are also congenital infections.
• 15:24In the US we screened all mothers
• 15:28before at the time of delivery for
• 15:31one Organism which used to cause the
• 15:34most trouble in the United States.
• 15:36We found no evidence of this Organism
• 15:39in any of the maternal specimens.
• 15:42Vaginal, placental,
• 15:45maternal blood or cord blood.
• 15:48Not likely it's coming from the mothers.
• 15:51We looked at 800 neonatal sepsis
• 15:55cases in several sites in the country
• 15:58and 400 cases of hydrocephalus,
• 16:01half of whom had a history of infection.
• 16:06Almost half of the infants under three
• 16:09months of age that came to us were still
• 16:13PCR positive to this one Organism,
• 16:17and 6% of the neonates with sepsis.
• 16:21And we actually were able to capture
• 16:24some true linkage cases where we
• 16:26could capture the Organism within a
• 16:30week of birth with clinical sepsis,
• 16:33treat the sepsis,
• 16:35appear to clear it from the periphery
• 16:39of the infant.
• 16:40Child's not febrile feeding well,
• 16:42no longer lethargic, goes home,
• 16:45but comes back a month or two later with
• 16:49continued infection in the brain and
• 16:51with the head enlarging from hydrocephalus.
• 16:55So what did we just do over 20 years ago,
• 17:00Frederickson Relman talked about
• 17:03the possibility of doing a sequence
• 17:07based identification of pathogens and
• 17:11proof that these molecules showed
• 17:14that an Organism caused an infection.
• 17:18Robert Koch,
• 17:20about 150 years ago had postulates
• 17:24that said to prove an infection you've
• 17:27also got the culture and Organism you
• 17:29have to be able to infect an animal with it.
• 17:33We've just violated all of those
• 17:39those strictures. Now here,
• 17:40if I'm standing in front of you,
• 17:44you all will think that's
• 17:46cutting edge and clever.
• 17:48But I didn't quite see covenants
• 17:50that in other settings.
• 17:52I just violated all the fundamental
• 17:55principles that good physicians were
• 17:58taught by their highly respected mentors.
• 18:01Working in other societies and in
• 18:05other settings is often challenging
• 18:07in ways that I can never predict.
• 18:11Well, now the So what question.
• 18:14I just spent millions of dollars
• 18:16of our tax good taxpayers money.
• 18:18It took years to finish all of this analysis.
• 18:22We're still working on some pieces
• 18:25of it and microbial genomic testing
• 18:29is very expensive and it's slow and
• 18:35none of the scales very readily.
• 18:39And these are medical emergencies.
• 18:41These children come in and they
• 18:44are at serious risk of dying and
• 18:46we need to make decisions quickly.
• 18:49So I'll walk you through what
• 18:51I like to call predictive,
• 18:54personalized public health.
• 18:57So what does that mean?
• 19:00We've done a lot of observation.
• 19:02We've done a lot of surveillance
• 19:06of these infections.
• 19:08And I'd like to be able to ask
• 19:10a mother two questions which
• 19:12they always know the answer to.
• 19:14Where are you from?
• 19:16And when did the infant get sick?
• 19:19I'd like to use our prior knowledge
• 19:23and experience then to say,
• 19:26well,
• 19:26what are the most likely organisms
• 19:29and most important point of care
• 19:32of the available antibiotics,
• 19:34what are the best ones to pick?
• 19:37Now if we're looking at post
• 19:39infectious hydrocephalus,
• 19:40which is how I backed into this,
• 19:43that's not the problem.
• 19:44If you want to cut this off,
• 19:46you have to address the much
• 19:49broader issue of neonatal sepsis.
• 19:52And neonatal sepsis is probably
• 19:56still responsible worldwide for well
• 19:59over half a million deaths a year.
• 20:03It's probably closer to 3/4
• 20:05of a million deaths.
• 20:07That's triple, I think,
• 20:09the number of deaths of any age for malaria.
• 20:14It's comparable to the number of global
• 20:17deaths from tuberculosis of any age.
• 20:20And I actually had the privilege
• 20:24of testifying to Congress on this.
• 20:27And the congressmen and women on that
• 20:31committee are really rather surprised
• 20:33because they haven't heard about this.
• 20:35And in my testimony,
• 20:37I suggested to them that the reason is
• 20:41that newborn infants dying in developing
• 20:44countries have had no political voice.
• 20:48If you look at the most
• 20:49recent studies I listed,
• 20:51a Cambodian study,
• 20:52and Nisa is a huge South Asian study.
• 20:56These are beautifully done studies
• 20:59on neonatal sepsis and they're
• 21:01able to recover an apparent
• 21:05pathogen in 2% of their cases,
• 21:082% why test at some point it's the
• 21:15traditional way we have gone about.
• 21:18Identifying pathogens is an abysmal
• 21:21failure in newborn infants for reasons
• 21:25that I'm also happy to discuss.
• 21:28But the loss of life here really demands
• 21:31that we do something very different
• 21:33from what we've done for many years.
• 21:38So to try to conceptualize of
• 21:42what would be an improvement,
• 21:47we've put all 60,000 villages in Uganda and
• 21:53fuse them onto the satellite climate grids.
• 21:57That's useful for a number of
• 21:58reasons that I'll get into,
• 22:00but it's also especially useful if we
• 22:04want to look at environmental effects.
• 22:07This particular disease
• 22:08has a huge rainfall effect.
• 22:11In terms of when these infants get sick,
• 22:14the neonatal warts fill up as the rains
• 22:17come in and empty out during the dry season.
• 22:20Here are 4000 mapped cases.
• 22:23Now, I don't have microbiology
• 22:25on 20 years of cases,
• 22:27but these are 4000 mapped cases.
• 22:30See my mouse?
• 22:32Yeah, of these infections
• 22:34and look at the clustering.
• 22:37So here's Lake Victoria and
• 22:40there are huge enormous swamps,
• 22:43papyrus swamps along the northern bank.
• 22:46The Nile starts here in the middle of
• 22:49this cluster and goes N to Lake Choga.
• 22:53Again, large swampy,
• 22:54wet areas on the southern and
• 22:57northern banks of Choga and here in
• 22:59this North Central region of Uganda.
• 23:11Let's see if it's unhappy with me.
• 23:14I'm very unhappy with me.
• 23:26Well,
• 23:29yeah, it's happy again.
• 23:33What about genomics?
• 23:34So do I need to know something
• 23:37about the hosts as I'm mapping the
• 23:40location and timing of disease?
• 23:45In case you missed it,
• 23:46the answer has to be yes.
• 23:48Every infectious disease that we
• 23:52contract as humans is actually a
• 23:55product of both the genomics of the
• 23:57Organism that give the Organism its
• 24:01characteristics and your genetic
• 24:03differences that both determine
• 24:06whether you contract an infection
• 24:09and how you do from an infection.
• 24:11Just think of COVID,
• 24:13there were many people who appeared
• 24:16to be asymptomatic or perhaps never
• 24:18got sick and I have two friends of
• 24:22mine who died within two days or so
• 24:25of contracting the viral infection.
• 24:27So the the current thinking is
• 24:31that we need to dual sequence
• 24:35the the genetics of bacteria or
• 24:39viruses as well as host to try to
• 24:43get a comprehensive picture of how
• 24:46to deal with infectious disease.
• 24:53So what to do? I I show up with all of our
• 24:56colleagues that we work with in Ambala,
• 24:59Uganda, and I propose this.
• 25:02And there is an awful lot of pushback.
• 25:05What are the concerns? First, privacy.
• 25:07How are we going to do genomic sequencing
• 25:12of hosts and protect the individuals?
• 25:16Second, Yeah, I get this one a lot.
• 25:19What about paternity testing?
• 25:23We could, if we wished, of course,
• 25:26determine who the parents are,
• 25:28if we had three samples.
• 25:30And lastly, in a society that's
• 25:33dealt with authoritarian regimes
• 25:35in the past like Idi Amin,
• 25:38there's concern for safety if the
• 25:40government has access or the public
• 25:43has access to genetic information.
• 25:46So we wrote a very comprehensive document.
• 25:49It's eight single space pages
• 25:51of text going through all of the
• 25:55issues we thought were important
• 25:57and how we might approach them.
• 26:00We would obviously not publish
• 26:03any names of patients.
• 26:05We'd use the birth dates
• 26:06but not publish them.
• 26:08We would use the village precise
• 26:11locations but not publish that.
• 26:13And I'll show you how we will
• 26:16go about Geo masking and the
• 26:18care that we offered that.
• 26:19So you can't re identify by
• 26:22knowing where someone came from.
• 26:25The genomes would not be individually
• 26:29sequenced and deposited.
• 26:30And then I thought,
• 26:34I'm an amateur at this,
• 26:36I need to run this by a pro.
• 26:39So I had come to meet Judy Illis,
• 26:41a very well known ethicist.
• 26:43She is in Canada.
• 26:45She has an extensive experience working
• 26:48with the Canadian First Peoples,
• 26:50the native population in Northern Canada.
• 26:53So I forwarded this to Judy.
• 26:55She was great.
• 26:56She went through every paragraph
• 26:58and she comes back and says you
• 27:00may be working with populations,
• 27:02but you have to figure out
• 27:04a way to return results.
• 27:06All right.
• 27:07So I approached colleagues in the
• 27:09government and we worked out that if
• 27:12we had findings that were important
• 27:14for various peoples within the country,
• 27:18that we'd work with government agencies
• 27:21to return those results properly.
• 27:25And then of course,
• 27:26we went to all the institutions
• 27:29to get their approval.
• 27:30The local IRB ethics boards,
• 27:33the US Ethics board,
• 27:35the government oversight board
• 27:37in Uganda for human research.
• 27:40And I floated it by NIH as well to
• 27:42make sure that all of the stakeholders
• 27:45on the compliance side had a chance
• 27:48to give us feedback and prove this.
• 27:51And if you look at those little grid squares,
• 27:56I looked for the ones that
• 27:58didn't have much population in
• 28:00the country of Uganda,
• 28:06country of Uganda,
• 28:07you see these sparsely populated areas.
• 28:10So some of these are game parks.
• 28:13More elephants and lions live there
• 28:16than humans for obvious reasons.
• 28:19There's also a large arid region in
• 28:23the northeast that has a a sparsely
• 28:26populated nomadic population,
• 28:28and we're going to come
• 28:29back to that in a bit.
• 28:30And we we in part of our proposal
• 28:34is that we would not map any points
• 28:37on any of the maps we're doing from
• 28:40any place with less than 1000 people
• 28:44in 120 square kilometer grid space.
• 28:50In the US, we don't map zip codes
• 28:55with less than 20,000 people for the
• 28:58same reason in Uganda we picked 1000,
• 29:02we picked a larger square mile area and
• 29:07then we actually jitter the points.
• 29:11So the points I just showed you on that
• 29:14map aren't actually the exact location
• 29:18where those villages are located.
• 29:21Here's a little picture of a colleague
• 29:23of mine and and a local resident
• 29:26hiking on a footpath over hills
• 29:28trying to find a village cluster
• 29:31where one of these infants is located.
• 29:33We think and all the people we've had review
• 29:38this think that that's adequate protection,
• 29:41the way we design this,
• 29:43so that we can publish maps
• 29:44and show you the clustering.
• 29:53We know a lot about ancient migrations in
• 29:57many parts of the world and of of course,
• 29:59in Africa. This is an old map of
• 30:02Jared Diamond who wrote Guns,
• 30:04Germs and Steel in Science 20 years ago.
• 30:08And Uganda is right sitting wrapped around
• 30:12the northern part of Lake Victoria.
• 30:15Here and in that part of Central
• 30:19Africa there are two main migrations.
• 30:21The Bantu expansion started
• 30:24around 5000 years ago, we think,
• 30:27and these people came up from
• 30:29the southern parts of Uganda,
• 30:31of of sub-Saharan Africa,
• 30:33and also came in from the southwest.
• 30:37Several thousand years later,
• 30:38there's a migration of Nilo
• 30:41Saharan people from the north.
• 30:43They come down, they literally
• 30:45seem to meet at the Nile River,
• 30:48which is a natural barrier.
• 30:53If you look at the clustering,
• 30:55the simplest way of clustering genomes,
• 30:59each of us has millions of differences
• 31:03at the single base pair level
• 31:06between our genomes if we sequenced
• 31:10up all of us sitting in the room.
• 31:13But if you look at the simplest
• 31:15way of doing that,
• 31:16just using a cluster technique,
• 31:20principal components to look at,
• 31:22how many groups could you
• 31:26statistically have in your data.
• 31:30This data gives you 4.
• 31:32There's a northern group in blue,
• 31:35There's a southern and
• 31:38southwestern group in red.
• 31:40There's a little bit of complexity
• 31:43here along the Kenyan border.
• 31:45We know that there's a Western
• 31:48migration from the Swahili coast that's
• 31:50been identified in recent years,
• 31:53but basically we pull out the
• 31:56ancient migration patterns trivially
• 31:59from doing the simplest version.
• 32:01This isn't even admixture analysis.
• 32:05The simplest version of clustering
• 32:08changes between chinos.
• 32:11So we've done a little more
• 32:13sophisticated effort at this.
• 32:15We've fit these points to a smooth model,
• 32:19but importantly,
• 32:20we're looking at the proportion
• 32:23of those groups.
• 32:24Because none of us are pure mixtures,
• 32:28we vary in our proportions
• 32:31between our ancestries,
• 32:33and what we find is that there are two
• 32:36groups that are very closely related.
• 32:38Those are Bantu,
• 32:41and then there's one Nilo Saharan group.
• 32:44The Nilo Saharan group is the largest
• 32:48distance difference distance between
• 32:50those two Bantu groups present.
• 32:54This all makes an awful lot of sense.
• 32:57Jared Diamond was reasonably correct
• 33:00in his estimates at the time.
• 33:03Without the genomic information.
• 33:06I'm also going to briefly introduce
• 33:09the second group of hydrocephalus.
• 33:12These are children with spina bifida.
• 33:15They're born with what looks
• 33:17like an open spine.
• 33:19This is a strongly genetically
• 33:22influenced malformation,
• 33:23but it's a gene by environment disease.
• 33:27We know that we can prevent most of
• 33:30this with adequate folate fortification
• 33:33of food or preconception vitamins.
• 33:36The rates in the US and in most countries
• 33:39that fortify food is quite low,
• 33:42about one per 2000 live births.
• 33:45The rate in Uganda is many,
• 33:47many multiples of that.
• 33:49I hope within the year we start to
• 33:52actually nail down the true incidence
• 33:54'cause we have to know that if
• 33:57we're going to be more effective
• 33:59about controlling the disorder.
• 34:04If we take that ancestral map and we look
• 34:09at other covariants such as poverty index,
• 34:12the two covariants that most
• 34:15associate with our mapping of
• 34:18spina bifida risk our poverty and,
• 34:22independently, nilo Saharan ancestry.
• 34:27As I tell my colleagues,
• 34:29this may not be true, but it's such
• 34:32an important finding to perhaps have
• 34:35stumbled into that if it's not true,
• 34:38we need to demonstrate that it's not true.
• 34:41If it is true, you all need to be asking
• 34:45us what are the specific pathways and,
• 34:49for instance, the metabolism of
• 34:52folate or insert another gene products
• 34:55that actually help tissues close,
• 34:58like the neural tube,
• 35:00and how might they be differently varied?
• 35:03In people who migrated from
• 35:06northern parts of Africa,
• 35:09the World Health Organization a
• 35:11few months ago passed a resolution
• 35:14that all member states needed to
• 35:17fortify or supplement folate to
• 35:20prevent these neural tube defects.
• 35:22Unfortunately,
• 35:23they left it up to each member
• 35:26state to figure out how to do it
• 35:29because the context is extremely
• 35:31different between societies.
• 35:34If I fortify wheat in a country
• 35:37where people don't eat wheat,
• 35:39I'm not doing anything that's
• 35:42that's helpful here.
• 35:44So how do you do community engagement and
• 35:49how do you handle the politics involved?
• 35:52I usually didn't think I needed
• 35:55to touch politics.
• 35:57I mean, I know something about medicine.
• 35:58I'm a pretty good amateur scientist.
• 36:01I just went to a talk by John and Kangasong.
• 36:06John was the former head of the
• 36:09African CDC until we made him AUS
• 36:13Ambassador at large from the US State
• 36:16Department to deal with global health
• 36:19security and diplomacy over health.
• 36:22And one of the things he emphasized
• 36:24to us is that if you can't manage
• 36:27to bring the decision makers and the
• 36:30political infrastructure to bear,
• 36:32you can't affect the impact that you
• 36:36need for any public health problem.
• 36:39Just look at the disaster that we
• 36:42created in our own society over
• 36:44our public health efforts for COVID
• 36:47vaccination masking. What a mess.
• 36:52During COVID,
• 36:53my colleagues and I created a very
• 36:57detailed model to try to predict
• 37:01within the continent of Africa
• 37:04and track COVID cases.
• 37:07Actually, it worked pretty well.
• 37:09Yeah,
• 37:09we could get pretty good estimates one
• 37:13week and actually two weeks ahead.
• 37:17And we work with what is the
• 37:20national planning authority.
• 37:22These are the folks that do the financial,
• 37:25agricultural and health planning
• 37:27for the country of Uganda.
• 37:30And we trained with one of their
• 37:34data scientists to do an excellent
• 37:36job of of of working with this
• 37:40model and doing predictions,
• 37:41scenario predictions of how
• 37:44policy change would affect COVID.
• 37:47Abraham Mullen.
• 37:48Guzi is a manager of technology and
• 37:51innovation for the country at two ministries.
• 37:54Joseph Muvwala is one of
• 37:56their lead economists.
• 37:58And they're actually here,
• 38:01these are screenshots on national
• 38:03television as they're explaining
• 38:05to their society why this is a
• 38:09way they can manage the pandemic.
• 38:12At a cabinet meeting their president thought,
• 38:16yeah that's exactly what we ought
• 38:19to be doing and they ran with
• 38:23this model 3 scenarios 1.
• 38:25Continued lockdown 1.
• 38:28Taking all restrictions away and
• 38:32one the intermediate course.
• 38:35And I I was there at the time.
• 38:38And
• 38:40predictions on the potential effects
• 38:42of the different interventions
• 38:44on the likely outcomes.
• 38:47The model analyzes a number
• 38:49of factors, including
• 38:52I don't think I'll ever see a
• 38:56a head of state explaining our
• 38:59computational modeling that we do
• 39:01here in the lab to an entire nation.
• 39:04But he uses this to justify changing
• 39:08his mind because partially restrict,
• 39:11partially coming out of lockdown
• 39:14appeared to be safe and fortunately
• 39:17the predictions were pretty good.
• 39:21So we had a fair amount of
• 39:24credibility after that with some of
• 39:26the decision makers in the country.
• 39:29And we've been talking with them
• 39:31and they've asked how can we partner
• 39:34with them to address a very high
• 39:37and stubbornly resistant rate of
• 39:39neonatal mortality in the country.
• 39:44We began weekly meetings by Zoom here
• 39:47from Yale and then several trips over
• 39:51to gather the stakeholders together in
• 39:54person and go over what we could do.
• 39:57And I wanted to focus on Preventable.
• 40:01Causes of neonatal death
• 40:05what we just closed the deal on two weeks
• 40:09ago is the agreement to do the following.
• 40:11It'll be led by the
• 40:14National Planning Authority.
• 40:15The Ministry of Health is on board.
• 40:17Their Ministry of Science and
• 40:19Technology is on board.
• 40:21The Kingdom of Usoga,
• 40:23which is shown here,
• 40:26which may have the highest rates
• 40:29of both neural tube defects and
• 40:32neonatal sepsis in the country,
• 40:34is on board.
• 40:37We're going to keep the specimens
• 40:40in the Ugandan biorepository
• 40:42that NIH had originally built as
• 40:44part of the H3 Africa program,
• 40:47and we're going to try to do as
• 40:49much of the sequencing as possible
• 40:52using in country scientists.
• 40:54What's the community here?
• 41:01It's a question.
• 41:03It's a complex question.
• 41:06Here's what the community
• 41:09partnership probably looks like.
• 41:12It involves midwives and nurses.
• 41:16It involves mothers who are advocates
• 41:19for children with this disease.
• 41:21Ruth here is a national organizer
• 41:25for advocacy for spina bifida.
• 41:29Lydia is on the National Nursing
• 41:32Council helping direct policy for
• 41:34nursing and mid midwives in the country.
• 41:38This man is one of the lead faculty members
• 41:42at the National University for Public Health.
• 41:47This individual is in charge of
• 41:51health policy for their planning.
• 41:54Abraham I showed you this individual
• 41:57is both one of their lead economists.
• 42:00He's also the Prime Minister of Musoga.
• 42:05I had a delightful couple of hours
• 42:07with their Minister of Science.
• 42:11Monica Musonero is a brilliant
• 42:14microbiologist.
• 42:15She's fascinated by all the
• 42:17things that we've been doing.
• 42:21This is the Minister of Health for
• 42:24the Kingdom of Busoga and on board
• 42:27as well is the Commissioner for
• 42:29Child Health throughout Uganda,
• 42:32the nation state of Uganda.
• 42:35Pamela and Babassi is a protege
• 42:38of Frances Fukuyama and she
• 42:41is a renowned urban planner.
• 42:43She is the chairwoman of their national
• 42:47planning and on February 11th,
• 42:51the Chaya Bazinga Day,
• 42:53the King of Busoga will be rolling
• 42:57out this project for neural tube
• 43:01defects and neonatal sepsis to
• 43:04the Kingdom Takes a Village.
• 43:08Malnutrition effects absolutely
• 43:12everything I just discussed,
• 43:15and stunting is the most obvious physical
• 43:19manifestation of severe malnutrition
• 43:22and undernutrition in early childhood.
• 43:25Worldwide,
• 43:25there are about 1/4 of a billion
• 43:29children who are malnourished to
• 43:32the point that they're stunted.
• 43:34And across Uganda,
• 43:36the current estimated stunting rate is 30%.
• 43:41That's not the worst society
• 43:43in sub-Saharan Africa,
• 43:44but these are pretty shocking numbers.
• 43:48And take a look at this.
• 43:49So this is probably the currently
• 43:52best stunt study I know of on the
• 43:57genetics of infant and child growth.
• 44:01Look where they pull their populations from.
• 44:05Yeah, it's from Western Europe,
• 44:07the United States, and Australia.
• 44:10I show this to my African colleagues,
• 44:13and they're appalled.
• 44:15But there's a serious lack of diversity
• 44:18in our analysis of even fundamental
• 44:22features of human existence,
• 44:24like growth from diverse people
• 44:27around the world.
• 44:29Here's 6000 children surveyed in Uganda.
• 44:34They start off around the median for
• 44:37size at birth, and within 24 months,
• 44:4030% of them are stunted in height.
• 44:44Look at the fallacy that this
• 44:48this brings you.
• 44:50So I'm going to circle that
• 44:52NE province in Uganda.
• 44:54The Karamajung lived there.
• 44:56These are tall,
• 44:58melodic people.
• 44:59They're related closely to the
• 45:02Maasai across the border in Kenya.
• 45:05If you look at height,
• 45:07there's a little area that they look stunted.
• 45:10But for the most part,
• 45:12they're stunting free and it's
• 45:16totally misleading.
• 45:17If you look at weight for height,
• 45:19they're starving.
• 45:22Fallacy is that if you use the
• 45:25wrong growth curves,
• 45:27very tall people will look average in
• 45:31height if they're seriously malnourished.
• 45:34Now,
• 45:35the African peoples are the most
• 45:38diverse genetically on earth,
• 45:40and if you look at recent studies,
• 45:43this is a gorgeous set of papers that
• 45:46Gurdasani has done over the last few years.
• 45:49Take a look at the following These
• 45:52are people from West Africa,
• 45:54Yoruba and Igbo peoples from
• 45:57Ghana from Nigeria.
• 45:59Take a look at this simple plot
• 46:02of admixture based off of the
• 46:04single nucleotide changes that
• 46:06we all have between our genomes.
• 46:09Now look at the East African peoples
• 46:12and the South African peoples
• 46:15like the Khosan or the Zulu.
• 46:18They have nothing at all like
• 46:20the West African group do.
• 46:22They They're very different
• 46:24and they've had many thousands
• 46:26of years of differentiation.
• 46:28Now look with how the World
• 46:31Health Organization provides
• 46:32the worldwide growth curves.
• 46:35They took a survey of wealthy
• 46:38children in the capital of
• 46:40Ghana in one neighborhood,
• 46:43measured their heights and weights.
• 46:46Then they took children from other
• 46:48continents, Brazil, India, Norway,
• 46:50Oman, the US and they created the World
• 46:55Health Organization growth curves,
• 46:58They don't actually apply
• 46:59to any child on Earth.
• 47:02So there's a really amazing malnutrition
• 47:06unit at the Jinja Children's Hospital.
• 47:10This is Harriet Nembuya.
• 47:12I've been to this unit several
• 47:14times and I haven't found
• 47:18a better malnutrition unit in my travels.
• 47:24Which brings us to a brief
• 47:26discussion of on growth and form.
• 47:29Now they teach this in that school.
• 47:32Well, they didn't do my day either,
• 47:35but if you're bored one night
• 47:36wandering around the medical library,
• 47:38you might find this.
• 47:39It probably hasn't been checked out a lot CRC
• 47:42Wentworth Thompson wrote this book in 1917.
• 47:45It's a little hard to read 'cause he
• 47:47knew of several different languages,
• 47:49and he sprinkled them in like just
• 47:53'cause he could, as he wrote it.
• 47:55But he looked at the growth and form
• 47:57of many different animal species,
• 47:59including humans.
• 48:00Take a look at what brains do.
• 48:05Your brains do most of their growth
• 48:08in the first three years of life,
• 48:10but your body keeps growing.
• 48:12So allometry is the study of
• 48:16these proportional differences
• 48:18between organ systems,
• 48:20and it has a really bad history
• 48:23associated with it in terms of what's
• 48:27called biological determinism.
• 48:28I used to think this was
• 48:30one of my favorite books.
• 48:32Stephen J Gould,
• 48:34the Harvard biologist's book
• 48:36on the Mismeasure of Man,
• 48:38and I used to it,
• 48:40used to be required reading in my laboratory.
• 48:43He looks at what Paul Broca,
• 48:46the neurologist in 150 years ago who
• 48:49named the speech area of the brain.
• 48:53And Broca said that there's a
• 48:55remarkable relationship between
• 48:57the development of intelligence
• 48:59and the volume of the brain.
• 49:01Broca had some axes to grind,
• 49:05In addition to wanting to prove
• 49:06that the French brain is better
• 49:08than the German brain.
• 49:12He was pretty hell bent on showing that
• 49:15male brains were better than female brains.
• 49:18So he did a fair amount of study,
• 49:20carefully done. Taking brains out at
• 49:24autopsy and weighing them carefully,
• 49:27he finds that male and female brains
• 49:30differ by about 200 grams. Now,
• 49:33Gould knew about Thompson's work and Gould.
• 49:38If my slide will advance,
• 49:41Gould corrects for height and age and weight,
• 49:47and he finds that there's he
• 49:50cuts that difference in half.
• 49:52When I read this as a grad
• 49:54student the first time,
• 49:55I remembered that the figure
• 49:58was probably close to 0.
• 50:00When I reread this many years later,
• 50:02I realized that Gould couldn't accept
• 50:05either his own or broke his data,
• 50:08so he just wrote that the
• 50:11difference wasn't there.
• 50:12I no longer recommend
• 50:14the book to my students.
• 50:16We looked at over 1000 scans of
• 50:20normal North American children,
• 50:23and indeed there is a difference in
• 50:26size between male and female brands
• 50:29of normal children proportioned by
• 50:31the demographics of North America.
• 50:34Indeed, Roca's difference is right there,
• 50:37and if you correct for height and weight,
• 50:40you get ghoul's difference.
• 50:42They were both right.
• 50:43What they didn't have a chance
• 50:45to do without imaging is look at
• 50:48the ratio of brain size to fluid.
• 50:50So you're all sitting here,
• 50:51it's about 6:00 and you're you
• 50:53have a good brain.
• 50:55So your brains are all at
• 50:57least 1400 grams or so,
• 51:00and they're floating in a couple
• 51:03of 100 CCS of spinal fluid and
• 51:05suspended in their little yellow sea.
• 51:08Your brains are weighing about 50 grams.
• 51:11And that's why you're kind of happy now,
• 51:13ready to have a meal and go to sleep.
• 51:16Don't bang your head is another
• 51:18lesson because it's kind of a
• 51:21delicate situation up there.
• 51:22But the universal featured that
• 51:25they were all perhaps looking for.
• 51:27Is that this ratio, a brain to fluid,
• 51:31is very tightly controlled,
• 51:32doesn't matter whether you're male or female,
• 51:35and it doesn't matter whether
• 51:36you're big or small.
• 51:38We don't understand it yet,
• 51:40but we then created childhood growth
• 51:44curves for normal childhood growth and
• 51:47we use it in our studies in North America,
• 51:50and we use it in our randomized
• 51:53clinical trials in Africa.
• 51:55Does it apply?
• 51:58So what about the rest of the
• 52:01world and its various peoples?
• 52:03Do we need different growth
• 52:05curves for their children?
• 52:09And I will wrap up in a few minutes,
• 52:12but most brains don't have access to imaging
• 52:15that we'd need to do brain growth curves.
• 52:18MRI is about the lowest risk and most
• 52:23expensive technology we've ever created,
• 52:26and the costs are around
• 52:29generating big fields.
• 52:31So they made the mistake of inviting
• 52:33me to give a plenary talk at the
• 52:36large worldwide meeting of MRI people
• 52:39and I just told them my thoughts.
• 52:42I said well, we haven't developed an
• 52:45approach to technology with a cost
• 52:48to benefit guides our image quality.
• 52:50We failed in major ways in developing
• 52:54imaging and we oversell to ourselves
• 52:57beautiful images that have no correlation
• 53:00with patient outcome and we failed to
• 53:03show the value of less expensive imagery.
• 53:06I've actually got a lot of positive
• 53:08feedback from this talk in the years since,
• 53:11which I was quite pleased to see
• 53:15this is an image from the 70s.
• 53:17My looked like it wasn't actually
• 53:20the 1st hemorrhage in the brain that
• 53:22I saw on ACT but it looked like this
• 53:25and it's a low resolution image.
• 53:28Here's a modern day high resolution
• 53:30MRI of the same kind of hemorrhage.
• 53:33Patient outcome won't be determined by
• 53:35how beautiful all those features are.
• 53:38We need to know where the hemorrhage
• 53:41is and know where to do the surgery
• 53:43that we do to get it out.
• 53:46So in in recent years we've during the
• 53:49pandemic we got one of the first of
• 53:52these portable low field units into
• 53:55that same hospital in Eastern Uganda.
• 53:57We're all wearing masks there that day.
• 54:00And most recently this year we assembled
• 54:03an entirely new type of device.
• 54:06This is an MRI that can give very
• 54:09high quality.
• 54:10So you can see in the image here on top,
• 54:14but it can be fully assembled,
• 54:16operated,
• 54:17maintained by the African engineers
• 54:20pictured here.
• 54:21The Dean of Engineering at Emberara,
• 54:23Jonas Abungalach,
• 54:24got his PhD in my lap and this
• 54:29assembly was covered by articles
• 54:32and Science and Nature.
• 54:34Francis Shen has a very nice article
• 54:37out on the ethics of this kind of
• 54:40low field MRI as it gets distributed
• 54:42around the world and his principles.
• 54:45Of the ones I started the talk with,
• 54:48Local Community Partnerships and
• 54:51Local Society Value,
• 54:54let me end with one set of thoughts
• 54:57for discussion.
• 54:58First,
• 54:59does Uganda now need a Bantu and
• 55:02an Elotic growth curve?
• 55:05My colleagues in the country very
• 55:07much want to see us do that.
• 55:10Would monitoring brain growth
• 55:12during renourishment help optimize
• 55:15the recovery of these children?
• 55:18I think that's a good thing to pursue.
• 55:21But I'm going to leave you all with
• 55:24a question. What shouldn't we do?
• 55:27And I'd like to hear your thoughts
• 55:31on that in discussion.
• 55:33Nobody does what I just showed
• 55:35you on their own.
• 55:37An awful lot of people in an awful
• 55:39lot of places have really poured their
• 55:41hearts and souls into this work,
• 55:44and really what I'm telling you
• 55:46today is representing all
• 55:48of their efforts. So thanks,
• 55:51everybody, and love to discuss.
• 56:00Would you like a chair? You've
• 56:01been standing up here for an hour.
• 56:02You good? I'm good. OK, so I'm gonna.
• 56:04I think Karen's gonna bring
• 56:06me up in a in a minute.
• 56:08Some of the questions from Zoom.
• 56:09In the meantime, we'll take
• 56:11questions for Doctor Schiff
• 56:12from the audience on this talk.
• 56:15Yes, Sir. Wait one second. Actually.
• 56:19So let's focus on Zoom. If you hear
• 56:22you just wait. If you wait until
• 56:23we get a microphone,
• 56:29hold it up close,
• 56:30Thank you for your for the talk.
• 56:33You spoke earlier in your talk
• 56:35about sort of the challenges of
• 56:39getting funding for your research.
• 56:41Could you give us a little more insight
• 56:43into that justifying taking U.S.
• 56:48tax dollars to fund research in in Africa and
• 56:53and you know how you justify that and so on.
• 57:00So there's two parts to that answer.
• 57:03First, to quote one of my colleagues here,
• 57:07if you can do something that's really
• 57:10worthwhile, just be relentless.
• 57:12I mean, I've had reject many more
• 57:15grants rejected than I've ever received.
• 57:19But you know, learning how to
• 57:22be compelling is important.
• 57:25Building a track record,
• 57:27starting with some small pilots,
• 57:29None of us ever got major funding
• 57:32without starting off with small steps.
• 57:37The value of doing work on important
• 57:41problems is that all of it benefits
• 57:46healthcare everywhere.
• 57:47Learning to diagnose an infection
• 57:50you can't grow in.
• 57:52Let's say a part of rural Africa is critical
• 57:56for the infections we can't diagnose here.
• 57:59Walk on to our neonatal intensive care unit,
• 58:02make friends with your favorite
• 58:04neonatologist and in a quiet
• 58:06moment it might take half a meal.
• 58:09In a quiet moment, say,
• 58:11how many septic infants do you
• 58:13never get a diagnosis on and you'll
• 58:16be pretty shocked at that number.
• 58:18It's well over 50%,
• 58:20and there's some good reasons for that,
• 58:22but you can apply that to adult sepsis.
• 58:25You can apply that to many cases of
• 58:29syndromic disease where it's not
• 58:31obvious what causes a syndrome.
• 58:34Sepsis, Meningitis, fever with rash,
• 58:38flu like illness.
• 58:40So these techniques are broadly
• 58:43needed in many, many settings,
• 58:46including here.
• 58:48We had to use them overseas,
• 58:52but you could have developed all of
• 58:56this with US based problems as well.
• 58:59It turns out since we published
• 59:03the Penny Bacillus finding in 2020,
• 59:06the 1st paper that we did that
• 59:09there have been six more recent
• 59:11reports of US cases same highly
• 59:15destructive Panibacillus infection.
• 59:17Most of those children have died.
• 59:20One or two went on to get hydrocephalus.
• 59:24We have no idea what the total number is,
• 59:28but I just presented this to NIH
• 59:31and they were sort of amazed that
• 59:35as we studied this disease that we
• 59:38didn't know anything about far away,
• 59:40that it's also here.
• 59:41Now that we know about it.
• 59:43I hope that answers your question.
• 59:45Was it?
• 59:46I think it answers a number of questions
• 59:48because what was, was it here?
• 59:51Was it identified by by DNA sequencing?
• 59:54Was it identified by
• 59:55by actually growth and culture? So
• 59:57most of the ones here grew out,
• 01:00:00we don't know the differences in the strains.
• 01:00:03And there's a number of things that
• 01:00:06I'd like to implement very quickly.
• 01:00:09In our in our African work,
• 01:00:14I think we may be able to get an
• 01:00:17echo and mute that. There you go.
• 01:00:21Got some technology going on here.
• 01:00:23All right. Did I do something wrong?
• 01:00:26No, it's OK. I was just something wrong.
• 01:00:29All right, All right. Very good.
• 01:00:32Next question, please. Yes, Sir.
• 01:00:40Hi, Dad. So,
• 01:00:43OK, so I'll let him have it,
• 01:00:44let him have it, Robert. Got it.
• 01:00:46So this is a genuine question.
• 01:00:47I actually haven't asked this before. So
• 01:00:51you mentioned Stephen Gould and the
• 01:00:57kind of the issues with results
• 01:01:01that you don't like and and
• 01:01:04discounting those do you worry
• 01:01:07about the potential ramifications
• 01:01:09of like you mentioned the Nilus
• 01:01:15Saharan people had a potential
• 01:01:19vulnerability to to his Penny Bacillus.
• 01:01:22Do you do you worry about the ramifications
• 01:01:24of finding out that that is
• 01:01:26indeed true or if you indeed
• 01:01:28need to use different growth curves for
• 01:01:31the not the Sahara and and Ponto people?
• 01:01:33Like especially in an area where
• 01:01:35there's it's very ethnically diverse
• 01:01:38and genetically diverse as you said.
• 01:01:40Do you worry about those kind
• 01:01:42of differences especially in a,
• 01:01:44as you mentioned a colonial science context.
• 01:01:48Good question.
• 01:01:50Sometimes you raise these kids.
• 01:01:52They do. OK,
• 01:01:55I think that it's important to be
• 01:01:59able to personalize our public health,
• 01:02:02But is everyone here recalls
• 01:02:05recently. How we do that
• 01:02:09critically determines whether
• 01:02:10we're effective or we just turned
• 01:02:14it into a political nightmare.
• 01:02:16In societies where the level of education
• 01:02:20is not what you would hope to have,
• 01:02:25the messaging becomes critical
• 01:02:27because people with can easily
• 01:02:31perceive this as something's
• 01:02:33wrong with them or create stigma.
• 01:02:37I can't create that messaging
• 01:02:40as some person from the US,
• 01:02:42but my colleagues are going to
• 01:02:47have that burden who live there
• 01:02:49and understand the culture well.
• 01:02:51And my physician colleagues really want to
• 01:02:55improve the medicine that they deliver.
• 01:02:59But I did offer a teaser to everyone
• 01:03:02about what we would not want to do.
• 01:03:07I'm negotiating right now to get a
• 01:03:10scanner for that malnutrition unit.
• 01:03:12I think we'll probably show that
• 01:03:16with renourishment we can get brains
• 01:03:20of these children to grow better.
• 01:03:23Do I want to personalize that?
• 01:03:29There's several questions I don't think
• 01:03:32I'll ever explore that I could explore.
• 01:03:35One is, is there a difference in
• 01:03:38brain size and brain growth between
• 01:03:41Nilotic versus Bantu peoples?
• 01:03:47It's a nil hypothesis to say no,
• 01:03:50every nothing's identical and
• 01:03:55somebody's going to have bigger
• 01:03:57brains than the other person. And it
• 01:04:02whatever medical benefit you might
• 01:04:05have from that, I think would be
• 01:04:08far outweighed by the harms that
• 01:04:10you potentially would create by
• 01:04:14stigmatizing a society with no,
• 01:04:17no realistic benefits. So
• 01:04:22it's a fine line and it's the judgement call.
• 01:04:26I have kids dying of infection and
• 01:04:29I could improve that death rate.
• 01:04:32Then it's worth stepping into the arena,
• 01:04:35especially if we can figure out, I mean,
• 01:04:38what gives you a predilection from disease.
• 01:04:40Go look at Casanova. Love that name.
• 01:04:42Look at Casanova's papers and his work.
• 01:04:44He summarizes it in those
• 01:04:46two papers in PNAS in 2015.
• 01:04:49What he finds is that you can have very
• 01:04:52specific predilections to certain infections,
• 01:04:56like staph aureus,
• 01:04:57because you have an interleukin
• 01:05:01or a cytokine protein that helps
• 01:05:05you defend against infection.
• 01:05:07And it's not quite right,
• 01:05:08the same way that sicklers get into
• 01:05:11trouble from sickle cell disease
• 01:05:13because they have one base pair
• 01:05:16different in their hemoglobin molecule.
• 01:05:19So what that means is we ought
• 01:05:23to be able to treat it.
• 01:05:25We replace protein compounds in hemophilias.
• 01:05:32Would we treat someday a person with
• 01:05:36an infection from staph aureus with a
• 01:05:40commonly defective protein by giving them
• 01:05:43a replacement protein as well as antibiotics?
• 01:05:48We don't do that today,
• 01:05:50but we're probably pretty
• 01:05:52close to being able to do that.
• 01:05:55So it's judgment call, Robert.
• 01:05:58And eventually,
• 01:06:00it all comes down, I think,
• 01:06:03to benefits and risks.
• 01:06:05And I do think as we get
• 01:06:08deeper into a genomic age,
• 01:06:10that we have to think pretty
• 01:06:12carefully about that.
• 01:06:16Could you, Steve, go back a little bit
• 01:06:18and and talk or mention you when you
• 01:06:20talked about Gould's comments on Broca?
• 01:06:22Sort of like, I remember like
• 01:06:247 things from medical school,
• 01:06:26but one of them was new problems
• 01:06:27of Eclomisphere, Ghosh Broca.
• 01:06:31And I'm fascinated by Google saying,
• 01:06:33no, I don't accept that.
• 01:06:34So he just said, no,
• 01:06:35I don't even accept my own data.
• 01:06:37This is in in terms of where
• 01:06:41science and bioethics meet.
• 01:06:42I've encountered this
• 01:06:43from time to time as well.
• 01:06:44And I've I've coined the phrase as we
• 01:06:46do this when I teach us don't fear the
• 01:06:48data because I have heard people say,
• 01:06:50well here is the data,
• 01:06:51but we're not going to talk about
• 01:06:52it because it doesn't bring us
• 01:06:55to the conclusion we want, right.
• 01:06:57Do you think some of that has gone
• 01:06:58on in terms of brain size and brain
• 01:07:00growth and is that could that possibly
• 01:07:02could the fear of the data direct
• 01:07:04how we move forward with the science?
• 01:07:05Of course.
• 01:07:07Should it?
• 01:07:09No.
• 01:07:11But
• 01:07:12I'm torn with these things like
• 01:07:14some of your fan clubs going
• 01:07:16he's got a test to take tonight.
• 01:07:19But I I I worry a great deal the power of
• 01:07:25these technologies to uncover facts which
• 01:07:29we may not be able to handle. I mean,
• 01:07:36look at the conflicts around the world.
• 01:07:37It doesn't take much.
• 01:07:39I think of Rwanda, in particular
• 01:07:43the Tutsis and the the Hutu.
• 01:07:47We're not even sure they were
• 01:07:49actually both ancestral people,
• 01:07:52but politically they were set up in a
• 01:07:56way that led to an enormous genocide
• 01:07:59of a population within about 90 days.
• 01:08:06I think we need to be very careful
• 01:08:09because we have tools which can
• 01:08:12literally weaponize our science.
• 01:08:14And this wasn't obvious to me when I
• 01:08:19started looking at things like the
• 01:08:21genomics of these children in Africa.
• 01:08:23But gradually I would sit with my colleagues,
• 01:08:27helps to spend a lot of time
• 01:08:29with your colleagues overseas.
• 01:08:30And I sort of looked at them and said
• 01:08:34we can cause an awful lot
• 01:08:36of trouble if we do this.
• 01:08:37And we all sort of looked
• 01:08:39at each other and said,
• 01:08:40yeah, let's not do that.
• 01:08:44I wish there was like the adult in the
• 01:08:47room who would have said long ago to us,
• 01:08:49do this, but don't do that.
• 01:08:51But there isn't. It's us.
• 01:08:53And I think these are burdens.
• 01:08:56Gould really disappointed me.
• 01:09:00I've read so much of his work.
• 01:09:02It's He's such a brilliant scientist.
• 01:09:05If you read Edward O Wilson's
• 01:09:09autobiography called Naturalist,
• 01:09:10you might worry a little
• 01:09:13about how difficult Gould,
• 01:09:16in a professional environment,
• 01:09:18might have been to the people around him.
• 01:09:21But many of us are not easy.
• 01:09:25And yeah, we do good work, I hope.
• 01:09:28But it's a trap.
• 01:09:30It's a trap that Ghoul felled into.
• 01:09:33He was a very politically active person,
• 01:09:38and he wasn't going to accept
• 01:09:40that result for anything.
• 01:09:42When I read it with, I think,
• 01:09:45a fair amount of care,
• 01:09:46I didn't appreciate it as a student.
• 01:09:50You'd appreciate what? I
• 01:09:50didn't appreciate his bias as a student.
• 01:09:53It took took losing hair and being
• 01:09:56in the business for a long time
• 01:09:59and to look at that and go, Oh no,
• 01:10:02look what he did and then he
• 01:10:04wrote it all down. But you know,
• 01:10:07we read these things for the message.
• 01:10:10How many of us look at a scientific paper
• 01:10:13and you know, you read the abstract,
• 01:10:16the first paragraph, the last paragraph.
• 01:10:18Is there anything in between that's
• 01:10:21worth your time before you move
• 01:10:23on to the next task of the day?
• 01:10:25But if I leave you any of you with a caution,
• 01:10:29it's be careful, and be careful
• 01:10:32what even the experts tell you.
• 01:10:38Other questions, things I can try to answer,
• 01:10:43Sir.
• 01:10:47Thanks, Doctor Schiff. I'm curious, I
• 01:10:51mean, you work with so many
• 01:10:55people from Uganda. Do you find like
• 01:10:57when when you're working
• 01:10:58with your African colleagues,
• 01:10:59you you have any like favorite
• 01:11:03examples of ethical disagreement
• 01:11:05where you just that are particularly
• 01:11:07intractable maybe that are grounded
• 01:11:09in cultural differences or different
• 01:11:13just, you know, starting from
• 01:11:15different ethical premises?
• 01:11:17Does that make sense? Yeah,
• 01:11:22I
• 01:11:26I'm a short white guy from the
• 01:11:28US and I didn't grow up overseas.
• 01:11:34And over the years I've worked very
• 01:11:38closely with a lot of both physicians
• 01:11:44and also with patients, families.
• 01:11:49And I think the one thing I
• 01:11:52come away with is there's a
• 01:11:56real universe have universality
• 01:12:00between doing medicine anywhere,
• 01:12:04and I find very much a lack of
• 01:12:10disagreement between myself
• 01:12:11and the colleagues I work with.
• 01:12:17Whereas we all sort of agree that certain
• 01:12:21science studies are way out of bounds.
• 01:12:25And the other thing I noticed is that
• 01:12:30mothers of sick infants are the same
• 01:12:33everywhere they care deeply for.
• 01:12:37And
• 01:12:41I I look at the women who bring their
• 01:12:44infants in and their willingness to
• 01:12:46let us try to enroll them in studies
• 01:12:50of their children's illnesses.
• 01:12:54And I think most of the cultural differences
• 01:13:00just melt away over young infants.
• 01:13:03It's probably why I can show you those
• 01:13:09examples of like government leadership,
• 01:13:14nursing leadership, child advocates,
• 01:13:17all in total agreement
• 01:13:20over certain things we do.
• 01:13:23And it's probably why that list
• 01:13:25of collaborators was so long.
• 01:13:29Infants or a universal currency.
• 01:13:33And if I were studying, I don't know,
• 01:13:37sexually transmitted disease of teenagers,
• 01:13:42I think it would be a much
• 01:13:45more difficult path to follow.
• 01:13:52Thank you. Other questions,
• 01:13:57they look tired and hungry. Say again,
• 01:13:59They look tired and hungry. They look
• 01:14:01tired and hungry. All right.
• 01:14:02Well, we gave them a little some of
• 01:14:04that just wet their appetite both for
• 01:14:06more sandwiches and more knowledge.
• 01:14:07This was a wonderful presentation.
• 01:14:09Doctor Schiff, thank you so much.
• 01:14:11Thank you all for coming. Thanks
• 01:14:16everybody. What's the
• 01:14:16talk about? What's the talk about?
• 01:14:20All right, we'll see you all in January. Have
• 01:14:23a good holidays.