- 7 months ago
In this scientific mystery, NOVA ventures to the front lines of medical research where scientists are scrambling to understand the strange new ailment popularly known as "mad cow disease." Highly infectious and incurable, this disease has claimed the lives of nearly a million cattle in Britain, and a variant is responsible for a handful of deaths in humans. Millions more people may have been exposed, and now the race is on to determine if we are on the brink of another deadly epidemic like AIDS or Ebola. What scientists are finding is making them rethink many fundamental assumptions about epidemiology and may hold startling implications for public health in the future.
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00:00Tonight on NOVA, a silent killer attacks the brain and claims its first human victims.
00:07He started hallucinating.
00:08He had very jerky movements.
00:11I think we all had to agree that this was something unexplainable.
00:15Past outbreaks offer chilling clues of how it spreads.
00:18It was clearly being transmitted from person to person by cannibalism.
00:23Is mad cow disease a threat?
00:25These agents are almost immortal.
00:28The Brain Eater.
00:50Major funding for NOVA is provided by the Park Foundation.
00:55A program dedicated to education and quality television.
01:02This program is funded in part by Northwestern Mutual Life,
01:06which has been protecting families and businesses for generations.
01:10Have you heard from The Quiet Company?
01:13Northwestern Mutual Life.
01:14And by the Corporation for Public Broadcasting and viewers like you.
01:20It appeared suddenly in England.
01:36A strange and horrific plague called mad cow disease.
01:39Almost overnight, cattle throughout the country became infected.
01:47Shaking uncontrollably, turning aggressive, and losing coordination.
01:53There is no cure for this mysterious disease.
02:00And it is always fatal.
02:07Desperate to halt the spread of mad cow disease, England destroyed nearly two million cattle.
02:13But it was too late.
02:14Since 1985, thousands of infected cows may have entered the food chain.
02:21It now seems certain that mad cow disease is crossing into a new species.
02:26Recently, an 18-year-old named Stephen Churchill fell ill with some very curious symptoms.
02:37He had very jerky movements.
02:40And he could suddenly decide to try and get up and walk when he wasn't capable of doing any kind of action,
02:48which would often result in him injuring himself or falling over if there was nobody around to help him.
02:56He started hallucinating.
02:58It started off as he'd be watching television and he'd get very enthralled in what was going on.
03:04If there was fire on the television, he'd feel as though he was burning.
03:07Or if it was like an underwater scene, he'd feel as though he was drowning.
03:11And then it got to a stage where he was just seeing things that just weren't there.
03:15At the time, the cause of Stephen's illness was a mystery.
03:21We saw CJD in a question mark written on the notes.
03:24And that was the first sign of they had maybe an idea of what it was.
03:28I found out that it was a very strange disease.
03:30But I also found out it was only really found in 50, 60, 70-year-olds.
03:34And although a lot of the symptoms seemed to fit, the age group didn't.
03:40Doctors thought that Stephen Churchill might have CJD,
03:43or Creutzfeldt-Jakob disease,
03:46a rare brain ailment in the same family as mad cow disease.
03:52Called spongiform encephalopathies, spongy brain disease,
03:57these illnesses riddled their victims' brains with holes.
04:02Did Stephen Churchill get CJD from infected beef?
04:06And if so, was the country on the brink of a human epidemic?
04:13An outbreak of a similar illness offered a chilling clue.
04:18Early this century, a strange new disease appeared in the highlands of Papua New Guinea.
04:23It was called Kuru, which means to tremble with fear in the native language.
04:28Within years, it killed thousands of the Foray people,
04:35but was unknown elsewhere in the world.
04:42In 1957, scientists traveled there to uncover the cause of this mysterious ailment.
04:48One of them, a young American pediatrician named Carlton Gajduszek,
04:54would one day win the Nobel Prize for this work.
04:56They found a population that was dying from this disease,
05:05but primarily affecting children of both sexes, equally, and young adult women.
05:12The first symptoms were a little in coordination.
05:16It'll stagger a little bit when they walked.
05:19Little by little, over a period of months,
05:21this became sufficiently severe so that they were unable to walk unaided, in time.
05:29The people were unable even to stand, and therefore became helpless.
05:36Most people with this disease died within nine months.
05:42Scientists investigated every possible cause of this illness,
05:46from malnutrition to genetic problems.
05:48The answer turned out, in fact, to be very simple.
05:53These people were cannibals.
05:56It was clearly being transmitted from person to person by cannibalism.
06:03Members of this tribe ate their dead relatives as an act of homage during funeral rites.
06:09In the course of cannibalistic ritual feasting,
06:18the body was cut up into parts,
06:21and the men reserved the best parts for themselves,
06:26and the best parts were muscle.
06:29The remaining parts of the body,
06:31including brain and pancreas and liver and kidney and intestines,
06:36were eaten by the women and the children.
06:39The disease was passed on as women and children ate the infected brains of their dead relatives.
06:46Many developed Kuru,
06:48and when they died, they were ritually eaten,
06:51escalating this deadly epidemic.
06:54This tragic cycle was broken when cannibalism among the Foray people ended in the 1960s.
06:59But the incubation period of this disease is so long that the last victims are still dying today.
07:07The solution to the way Kuru was passed from human to human,
07:13together with a number of laboratory experiments conducted over the years since,
07:17have a number of years since,
07:18have, uh, without any question, uh, brought persuasive evidence to the idea
07:25that infection can be transmitted by feeding.
07:33Cannibalism may be the cause of England's mad cow epidemic, too.
07:37Cannibalism among cows and sheep.
07:46Scrapey is similar to mad cow disease.
07:49But it attacks sheep.
07:51It's called Scrapey because infected sheep scrape their skin raw.
08:00Scrapey has existed in England for at least 200 years.
08:03But it has never crossed into cows.
08:08So how did cows get mad cow disease,
08:11known by its medical name as bovine spongiform encephalopathy, or BSE?
08:19Just as with Kuru, food was the culprit.
08:23For several decades, cattle feed had included a cheap protein supplement
08:27made from the carcasses of other animals,
08:29including sheep and cows.
08:33BSE probably arose when sheep infected with Scrapey
08:38or cows with BSE were turned into feed.
08:44The feed then infected other cows that ate it.
08:47And when those animals died,
08:49they were fed back to more cows,
08:51creating a rapidly escalating epidemic.
08:54It was a kind of cattle cannibalism,
08:57frighteningly reminiscent of Kuru.
09:00And for two years after BSE was known,
09:03infected cattle were still allowed into England's food supply,
09:07raising fears that people might get BSE.
09:12To assess that risk,
09:13the British government called upon the scientific community.
09:16Back in 1988, it was very difficult to be confident in one's recommendations.
09:24The amount of information that we had about spongiform encephalopathy was very small.
09:30We knew there was this disease in sheep, fairly widespread, called Scrapey,
09:34which had been around for 100 to 200 years.
09:38It didn't seem to be causing a great deal of problems in the human population.
09:43So we based our conclusion that the chance of transmission to humans was remote
09:49on the long experience of Scrapey.
09:51As an extra precaution,
09:54the British government banned the practice of feeding cows and sheep back to each other.
10:00And cattle already showing signs of BSE
10:03were excluded from use in human food and destroyed.
10:07But these measures left people at risk.
10:10BSE had such a long incubation period
10:15that cattle that appeared healthy but were actually harboring the disease
10:20could still be sold and used in human food.
10:26And the government continued allowing many organs where BSE accumulates,
10:31including the brain and spinal cord,
10:33to be added to British meat products.
10:35Eventually, the British government called for the removal of these parts
10:40from all carcasses being slaughtered.
10:47But no one knows the extent to which infected cattle
10:50and contaminated beef products entered the food chain.
10:53I've often reflected as to whether we wrote our report in too reassuring way
11:01and in some way this dimmed the urgency which was necessary.
11:08And obviously, one regrets that.
11:12Critics also charged that the interests of industry were placed above public health.
11:17You may wonder why we were not more alarmist in our report,
11:21but you must remember that at that time
11:23we were dealing with a very rare disease in cattle.
11:26A human disease is and has remained very rare.
11:30Most people had never heard of it.
11:32And if we had been too alarmist,
11:35we were in danger of upsetting the whole of the meat industry
11:39in Britain and elsewhere in Europe.
11:42Outside of England, restrictive steps were taken.
11:45The European community banned the import of most British cattle,
11:52although packaged meat products were still allowed.
11:58The United States also imposed a ban on British cattle.
12:02This country did a couple of things immediately.
12:06It first of all banned, as did most countries, all countries perhaps,
12:11the importation of living animals from Great Britain.
12:17Going one step further than Europe,
12:19the United States banned all British beef products in 1989.
12:26Meanwhile, the Department of Agriculture began tracking down
12:30the several hundred British cattle
12:31that had been imported to the United States
12:34just before the ban went into place.
12:37We pulled the records for the 496 that were imported.
12:41And we had our field veterinarians trace those out,
12:45locate the farms where they were now residing,
12:48and then monitor those, check them every six months,
12:51where they would go out, talk to the owner, check for signs.
12:54Those cattle never showed any symptoms of B.S.E.
12:58And most have been bought by the Department of Agriculture and slaughtered.
13:03But imported British cattle was only one issue.
13:09The question was brought up,
13:11could American cattle be harboring their own native strain of B.S.E.?
13:16In 1985, in the Wisconsin town of Stetsonville,
13:24mink, being raised for fur,
13:26came down with a rare spongiform encephalopathy
13:29like mad cow disease.
13:32Almost overnight, they started showing classic symptoms of the disease,
13:37such as loss of coordination.
13:40They soon became listless and died within weeks.
13:43The disease wiped out thousands of mink.
13:48Richard Marsh, a veterinarian at the University of Wisconsin,
13:53was called in to figure out what had caused the epidemic.
13:57Marsh thought that something in the feed was spreading the disease.
14:00Now deceased, Marsh used to work in Paul Brown's lab at NIH.
14:06Since mink are fed carcasses,
14:09they are voracious carnivores,
14:11the interest very quickly led to the idea
14:16that the carcasses were at the base of it
14:19and that they were getting infected through sheep,
14:22specifically scrapie in sheep,
14:24and sheep carcasses were being fed to mink,
14:26so it made sense that sheep were the source of mink encephalopathy.
14:32But Marsh began to suspect that on this farm,
14:35scrapie was not the cause.
14:37No sheep had been fed, but downer cattle carcasses were fed.
14:45Downer cattle are called downer cattle because they lie down,
14:49because they're sick and they die.
14:51And many different diseases cause this picture in cattle.
14:56And the thought was, well, here you've got an outbreak of spongiform encephalopathy in mink
15:00that apparently had been exposed to downer cattle and not sheep,
15:05and maybe the cattle were the source of the outbreak.
15:09The mink outbreak convinced Marsh that a low-level native strain of BSE exists in the United States,
15:17but was going undetected.
15:18So the idea that BSE might exist in this country,
15:24either producing a disease that wasn't recognizable as BSE,
15:29or existing as a silent infection,
15:32was one that we had to seriously consider.
15:36And because of Dr. Marsh's theory,
15:38in 1993 the USDA started to do surveillance on downer cows.
15:43We've tried to approach it from a scientific standpoint and say,
15:47well, hey, if there is such a thing, let's look for it.
15:50To date, we've looked at over 6,100 brains and found no evidence of BSE.
15:56So that's a pretty good piece of evidence that this is not the case in the U.S.,
16:03but it's not proof.
16:05Still no cases of BSE have ever been found in the United States.
16:09But in England, throughout the 1990s,
16:13BSE was spreading fast, and not just in cows.
16:20British house cats started contracting the disease from beef and pet food.
16:26Like people, cats have never been susceptible to scraping.
16:32It was certainly concerning when domestic cats developed a spangiform encephalopathy,
16:37and we now know that that is BSE that was acquired by these domestic cats
16:44and now by quite a few wild cats kept in zoos
16:49and some other wild animals kept in zoological gardens.
16:54And so that really indicated that BSE had a quite different host range than scrapie.
16:59It was infecting different species that had not gone down with scrapie in the past.
17:03So that was certainly, of course, a concern for me.
17:06Of course, that doesn't tell us that humans are going to be at any higher risk,
17:09but it does tell us that BSE is rather different than scrapie.
17:14In many illnesses, including scrapie,
17:17biological differences between species prevent diseases
17:20that originate in one kind of animal from infecting another.
17:25This is known as the species barrier.
17:27For example, scrapie has existed for centuries,
17:31but no person has ever gotten scrapie from eating lamb.
17:36Unlike scrapie, though, BSE has proven highly transmissible,
17:41crossing into nearly every species exposed to it.
17:45For so many animals, the species barrier against this new disease
17:49was turning out to be weak,
17:51and there was no way to know whether it would be for people, too.
17:54It really is quite an unpredictable phenomenon.
17:58By and large, we tend to think that animals
18:00that are more closely related in evolutionary terms
18:03are going to be easier to transmit the disease to.
18:06But it's not always like that at all.
18:08For instance, it can be extremely difficult
18:09to transmit the disease between mice and hamsters,
18:12which are quite closely related species.
18:14It seems to be relatively easy to transmit BSE to mice,
18:17which are quite distantly related species.
18:20So, you know, there are some very strange rules operating here.
18:24When a spongiform encephalopathy crosses a species barrier,
18:30a frightening phenomenon can take place.
18:34As the disease passes among members of the new species,
18:38it can become stronger and more virulent,
18:40and its incubation time can shrink.
18:44Then, this new type of disease may be able to infect other species
18:48that were not previously susceptible.
18:50We've certainly known since the mid-1970s
18:55that when scrapie infection is transmitted to
18:58and passaged within a new species,
19:00that strain characteristics and disease characteristics can change,
19:04and that a phenomenon analogous to mutation can occur,
19:09and that as a result of that, you can generate
19:11a strain with new properties, with new characteristics,
19:14with altered neuropathology,
19:16and even with an altered host range.
19:19Let's assume that BSE is the result of rendered,
19:25recycled scrapie in the food chain of cattle.
19:30There is not a shred of evidence to date
19:33that scrapie has ever caused CJD in humans.
19:37But, scrapie passaged or going into cattle
19:45might change the host range of the infection,
19:49and therefore, we cannot predict
19:52whether BSE would be or would not be infectious for humans.
19:58We, of course, had no way of knowing at that time
20:02whether the BSE agent was exactly the same as the scrapie agent.
20:06Work since has shown that it does actually perform
20:11in a slightly different way to the scrapie agent.
20:17This news was alarming.
20:19If BSE has a different host range from scrapie,
20:23could it infect humans, turning their brains to sponge?
20:30Answering that question was difficult
20:32because these strange diseases do not behave
20:35like conventional illnesses.
20:40Most infectious diseases are caused by bacteria or viruses,
20:46tiny microbes that can only be seen under the microscope.
20:51Bacteria and viruses contain genetic material,
20:55nucleic acid such as DNA.
20:58Nucleic acid is the essential ingredient of life
21:00and allows organisms to reproduce.
21:02Bacteria and viruses cause disease by spreading toxins
21:10or damaging their host.
21:13But spongiform encephalopathies seem to operate differently.
21:16Unlike bacteria and viruses,
21:19they provoke little or no immune response.
21:23Signs that the body is fighting infection, such as antibodies.
21:29And they have another strange characteristic.
21:32In the 1960s, scientists found that radiation,
21:35which kills viruses and bacteria by destroying their genetic material,
21:39has little effect on spongiform encephalopathies.
21:44They appear to defy the rules of biology.
21:47These agents are almost immortal.
21:53They resist alcohol.
21:54They resist boiling.
21:56They resist hospital detergents.
21:58We thought it would be interesting to see what would happen
22:03if we buried some of these agents.
22:07And so I ground up some scrapie brain and mixed it with soil,
22:13put it in a flower pot, enclosed it in a cage,
22:16and used my own garden as a burial site right here.
22:21And what we found was that a good deal of the infectivity
22:25remained in the soil after three years.
22:29We exposed it to temperatures that turned it to ash.
22:35And it did not entirely kill the agent.
22:42And so every known pathogen of man
22:46would have been destroyed by this process,
22:50and this was not.
22:53So if these diseases don't behave like other pathogens,
22:57what are they?
23:01Scientist Pat Murs discovered a tantalizing clue
23:04in her New York laboratory.
23:08Using an electron microscope,
23:10which can magnify up to 100,000 times,
23:13she was looking for the infectious agent that causes scrapie.
23:18At that time, most believed the killer was a slow-acting virus.
23:24But her discovery pointed scientists in a new direction.
23:27She detected these hazy threads in the brains of animals infected with scrapie.
23:37They did not appear in the brains of healthy animals.
23:42Murs thought these fibers could be a sign of scrapie,
23:46CJD, and Kuru.
23:47But each of these strands contains millions of particles,
23:52far too small to be identified even with the electron microscope.
23:58A different technique was needed.
24:00What we wanted to look for was what was unique about a sample from the diseased brain
24:10that was not in the normal brain.
24:13What component, what molecule would be in that diseased brain
24:18that was never in the normal brain?
24:20And so I did some experiments where I looked at proteins
24:25and separated these proteins using a gel
24:27to separate them by their size.
24:30And they give little different bands on the gel.
24:33And when I did that,
24:35I didn't really expect to find anything right off the bat.
24:39And after one of the experiments,
24:42I went into the darkroom to develop the film.
24:44And I was very surprised when I saw this.
24:51And I knew when I saw this gel
24:53that this had to be it.
24:56There's a fuzzy band that's here in the gel
25:00that's in each of the three samples from the diseased brain.
25:03And it's not in the samples from the normal brain.
25:07And this is exactly what we had been looking for.
25:10We and everybody else had been looking for some sort of a key,
25:13some kind of a molecule that we could say
25:16was in the diseased brain and not in the normal brain.
25:20And that really forced us to conclude
25:22that this protein is part of the agent,
25:25in fact, might be the only component of the agent.
25:32This band of protein appeared to be the only difference
25:35between the diseased brains and the normal brains.
25:40They called it the PRP protein.
25:43Finding it didn't solve the mystery, though.
25:48It deepened it.
25:50Because no one thought a protein could be an infectious agent.
25:56Apart from water,
25:57our bodies are composed largely of proteins.
26:01There are thousands of different kinds of proteins,
26:04aiding in everything from digestion to thinking.
26:08But proteins contain no genetic material,
26:12no nucleic acid, which would allow them to reproduce.
26:16So how could a protein multiply and cause disease?
26:20To the best of my knowledge,
26:23all infectious agents, all pathogens,
26:26require the participation of nucleic acid
26:30in order to multiply to replicate.
26:32The idea, therefore,
26:35that replication could occur
26:37without nucleic acid is heresy.
26:42We couldn't figure out
26:44how could a protein replicate
26:47if it doesn't have a nucleic acid.
26:49The answer had been suggested decades earlier,
26:54but dismissed as too outlandish.
26:57I started thinking about several years before
27:01when I had been doing a literature review
27:04and looking in some journals in the library
27:07at a paper,
27:08and I was looking actually up one paper
27:12that was written about the nature of the scrapie agent,
27:15and when I went to photocopy it,
27:17on the second page of that paper,
27:19there was another paper,
27:20and it was by a mathematician named J.S. Griffith.
27:25And in this paper,
27:26he talks about self-replication and scrapie,
27:30which is one of these diseases.
27:31And he outlines three ways
27:33that a protein alone
27:35could replicate and cause disease.
27:42Now, he came up with the idea
27:44that you would have two different forms of the protein.
27:47One was abnormal, disease-causing,
27:50a rogue protein, if you will,
27:52and the other was a normal protein,
27:54that would be in the cell or in the brain
27:57of a normal person.
27:59And the essential part of the theory
28:01was that the abnormal form of the protein
28:04could bind to the normal form
28:05and convert it,
28:07change its structure
28:08to make it an abnormal
28:10or a disease-causing protein.
28:12And now you can see
28:13that if one molecule binds to another molecule
28:16and converts it,
28:17now you have two molecules of abnormal protein,
28:19and two can bind to two more
28:21and have four,
28:22and so on and so on
28:23until you have thousands and millions
28:25of abnormal proteins in the brain.
28:27And pretty soon then,
28:28you have disease.
28:29You have so much abnormal protein in the brain
28:31that it would cause disease
28:33and cause neurons to die.
28:34The most amazing thing
28:47was that the paper was published
28:48in 1967.
28:51He was a mathematician,
28:53wrote this one paper,
28:55never published anything again in Scrapey.
28:57The insight was really very astounding
29:01that someone back then
29:03with so little information
29:04could see a way
29:06that a protein
29:07could be an infectious agent.
29:11Since then,
29:12the idea has been taken up
29:13by many scientists,
29:15most notably Stanley Prusner.
29:18He and others found
29:20that there are two types of PRP protein
29:22in the brain,
29:23just as Griffith predicted.
29:27One is a normal protein
29:30found in all mammals.
29:37The other is a disease-causing form
29:40of the protein
29:41called a prion,
29:43a term coined by Prusner.
29:46The prion is chemically identical
29:48to the original protein,
29:50but it has a different shape
29:52which makes it so stable
29:53that it resists heat
29:55and disinfectants.
29:59It appears to have
30:01no genetic material,
30:02so radiation does not harm it.
30:06Once in its abnormal form,
30:08this new molecule
30:09seems to have the ability
30:10to corrupt any healthy
30:12PRP proteins
30:13that it comes into contact with,
30:15turning them into prions too.
30:20This is not replication,
30:23it's conversion.
30:24It's a very strange observation
30:28that you have these two
30:29quite different forms
30:32of the same protein
30:33with quite different properties.
30:36One of them
30:37is a killer.
30:39If this protein
30:40is present in your brain,
30:42you're in serious trouble.
30:43The other one
30:43is a normal constituent
30:45of all our brains.
30:46And obviously,
30:47understanding how one
30:48converts into the other
30:49and in the longer term
30:51how to stop it
30:51is a tremendous puzzle.
30:56While scientists
30:57are still piecing
30:58that puzzle together,
31:00they have found
31:00that prions
31:01can link up
31:02in long,
31:03indestructible chains
31:04that accumulate
31:05in the brain.
31:07There,
31:07they kill cells,
31:09creating the holes
31:10that turn the brain
31:11to sponge.
31:15If correct,
31:17the prion
31:17or protein-only hypothesis
31:19would be revolutionary,
31:21a phenomenon
31:22unheard of before
31:23in biology.
31:25I very strongly believe
31:27in the protein-only hypothesis.
31:30But it remains
31:31unproven
31:32and controversial.
31:34Some believe
31:35that prions
31:35are not the cause
31:36of disease,
31:37but the byproduct of it.
31:40Others think
31:40the infectious agent
31:41might turn out
31:42to be a virus
31:43or something similar.
31:45It's genetic material
31:46hidden in a protective
31:47coat of protein.
31:49The idea
31:49that it is
31:50an infectious protein
31:51is an exciting
31:52and curious idea,
31:54but it's one
31:54which I do not accept.
31:55This would be
31:56a novel biological mechanism.
31:59It's been difficult
31:59to accept
32:00because of that,
32:02because there's
32:02no precedent.
32:05But since no genetic
32:06material has been found,
32:09the protein-only hypothesis
32:11is gaining support.
32:12This has been an extremely
32:14controversial area
32:15of science.
32:17Prions are novel
32:18infectious agents,
32:20and there's been
32:22a very rapid evolution
32:23of ideas.
32:25And I think BSE
32:26has arrived on the scene
32:28in the midst
32:29of this scientific controversy.
32:31The answer
32:32is still not known
32:34with certainty,
32:35but more and more
32:37it looks as though
32:38the protein-only hypothesis
32:39will turn out
32:41to be correct.
32:43While the idea
32:44continues to be debated,
32:46the 1997 Nobel Prize
32:48for Medicine
32:48was awarded
32:49to Stanley Prusner
32:50for his pioneering work
32:52on prions.
32:52What started out
32:55as heresy
32:56had become mainstream.
32:59But now,
33:00another issue
33:00was taking center stage.
33:03The burning question
33:04became,
33:05can BSE transmit
33:06to humans?
33:07And are we going
33:08to see an epidemic
33:08of human disease
33:09following exposure
33:10to BSE?
33:13It was an urgent question,
33:15and a special
33:15scientific team
33:16was formed
33:17to look for clues
33:18that mad cow disease
33:19might be passing
33:20into the human population
33:22in the form
33:23of an illness
33:23like CJD.
33:25But no one knew
33:26exactly what
33:27they were looking for
33:28or what they would find.
33:36One member of the team
33:37visited CJD patients
33:39before they died,
33:41looking for any new
33:43or unusual form
33:45of the disease.
33:47I would travel
33:48throughout the whole
33:49of the country
33:49to see patients
33:50with Christopher-Yakob disease
33:51as the geographical
33:52distribution
33:53is completely random.
33:56Most patients
33:57with Christopher-Yakob disease
33:58by the time
33:59that I visit them
34:00are severely demented,
34:02so they're unable
34:03to communicate.
34:04They usually mute,
34:06lying in bed,
34:08unable to move.
34:09And they have
34:10jerking movements
34:11of their limbs,
34:12what's called
34:12myoclonus.
34:14They can also
34:15not infrequently
34:16be blind,
34:17and even though
34:20they can't see,
34:21their brain
34:21is producing
34:22hallucinations,
34:23which can make
34:24them look very frightened.
34:30Another member
34:31of the team
34:31had the job
34:32of examining
34:33the brain
34:33of anyone
34:34suspected of dying
34:35of CJD
34:36to look for links
34:38with mad cowardicees.
34:41But a CJD autopsy
34:43requires special precautions.
34:50I've now changed
34:51into the clothes
34:52I'll wear
34:52to do an autopsy
34:54in a case
34:54of suspected CJD,
34:56and these garments
34:58are disposable
34:59because they will be
35:01incinerated
35:01after the autopsy.
35:02These are the gloves.
35:07On the top
35:08is a chain-mail
35:10handpiece,
35:12and this is
35:15flexible
35:16and allows my hand
35:17to be protected
35:18from any cuts
35:19while the autopsy
35:21is being performed.
35:22I wear another pair
35:23of rubber gloves
35:23on top of this
35:24just to make the whole
35:25thing as waterproof
35:26as possible.
35:29And this is the
35:30helmet.
35:31I'll just put it on.
35:32The instruments
35:42that I use
35:43in the post-mortem room
35:44and the instruments
35:45the technicians
35:45use in our
35:46dedicated laboratory
35:48really be regarded
35:49these as being
35:50permanently contaminated,
35:52so we use those
35:53for CJD cases alone
35:55because there's
35:56no effective way
35:58of guaranteeing
35:59decontamination
36:00in this disease.
36:02A third member
36:05of this new
36:06surveillance team
36:07was on the lookout
36:08for the emergence
36:09of any new patterns
36:10of CJD cases.
36:12There are a number
36:16of possible things
36:17we could look for
36:18including a change
36:19in the number
36:19of cases
36:20that might be
36:20identified every year,
36:22for example,
36:23looking at a change
36:24in occupation
36:26to see whether
36:26the people
36:27who were in contact
36:28with cows
36:29or with BSC tissue
36:30might be more at risk
36:32and also to look
36:33at any change
36:34in the age
36:35of the patients
36:36or the other
36:36clinical features
36:37and finally
36:38to look at
36:39the neuropathology
36:40to see if that
36:41had changed
36:41in any way.
36:43We really had
36:44no idea
36:44what we were
36:45looking for.
36:46Our mission statement,
36:48if you like,
36:48was to identify
36:49every case of CJD
36:51in Britain
36:52and to study
36:53the clinical
36:53and pathological
36:54features
36:55to monitor
36:55any change.
36:57In the spring
36:58of 1995,
37:00changes began
37:00to emerge.
37:02At 19,
37:03Stephen Churchill
37:04died from what
37:05doctors thought
37:06was CJD.
37:07This puzzling
37:09case of CJD
37:10in someone so young
37:11caught the attention
37:12of the surveillance
37:13team.
37:15June 1995,
37:17we heard about
37:18one young patient
37:20with CJD,
37:21a teenager
37:22with CJD,
37:22and this was
37:23clearly very unusual.
37:25And then,
37:25a few months later,
37:26we heard about
37:28another case
37:29in another teenager.
37:31And this was
37:32clearly exceptional.
37:34In December,
37:35we began to
37:37be referred
37:38a number of other
37:39younger patients
37:40with CJD
37:40in their 20s
37:41and 30s
37:42with a very unusual
37:43clinical presentation.
37:45They didn't show
37:46the typical appearances,
37:47which is
37:48in the brainwave
37:49recordings
37:50that we see
37:51in Spirotic
37:51Crips-Fly-Jakob disease.
37:53This is a brainwave
37:55recording from
37:55a patient
37:56with
37:56Spirotic
37:57Crutz-Fly-Jakob disease,
37:59and it shows
37:59the classical
38:00appearance
38:00associated with
38:01CJD.
38:03These sharp
38:05waves
38:05are occurring
38:06all across
38:09the tracing,
38:09coming from
38:10the various
38:10parts of the
38:11brain,
38:12and they occur
38:13regularly,
38:14usually once
38:15or twice
38:15every second.
38:18However,
38:18in the new
38:19patients,
38:20none of them
38:21had that
38:22classical appearance,
38:22and what we saw
38:24was just
38:25slow waves.
38:27They didn't show
38:28the typical
38:29appearances
38:29associated with
38:30the sporadic
38:31form of the
38:31disease.
38:33The first time
38:34I saw
38:35the new
38:36variants of
38:36CJD
38:37was in a
38:37brain biopsy
38:38from a young
38:39patient,
38:39and I can
38:40remember being
38:41very struck
38:42even in this
38:43very small
38:43piece of tissue.
38:45The changes there
38:46were very different
38:47from anything
38:47that I'd ever
38:48seen before.
38:50This was the
38:51first confirmed
38:52case of a new
38:53type of CJD.
38:56But what had
38:57caused it?
38:58Somebody came
38:59down with a
39:00questionnaire and
39:01asked us questions
39:02about lifestyle
39:03and eating habits,
39:04where we've been
39:05on holidays,
39:06that sort of
39:07thing.
39:07Obviously,
39:08with Stephen being
39:0819,
39:09mum and dad
39:09knew exactly
39:11the medical
39:12treatments he'd
39:12had,
39:13eating,
39:14that sort of
39:14thing,
39:14because he was
39:14still living at
39:15home at that
39:15time.
39:17Steve was
39:17no different
39:18to anybody
39:18else.
39:19He didn't
39:19have any
39:20operations that
39:21would have
39:21put him at
39:21risk.
39:22He didn't
39:22eat anything
39:23strange.
39:24He was a
39:25normal child,
39:27and he was
39:28a normal 18-year-old
39:29up until he
39:30became ill.
39:31He did eat
39:31beef burgers,
39:32but he ate
39:33sausages.
39:34He ate all
39:35sorts of
39:35things, no
39:37more or no
39:37less than
39:38most other
39:39people, so
39:39completely
39:40normal in
39:40that respect.
39:43Eventually,
39:43other cases
39:44like Stephen's
39:45emerged.
39:47And to
39:47confirm their
39:48suspicion that
39:49they had a
39:49new form of
39:50CJD, the
39:51team used a
39:52computer to
39:53compare brain
39:54slides from the
39:55randomly occurring
39:56or sporadic form
39:57of CJD, and
39:59the new cases.
40:01The microscopic
40:02holes that
40:03accumulate in the
40:04brain were
40:05outlined in red.
40:07When we first set up
40:09the project, we
40:10were anticipating
40:11that perhaps the
40:12changes would be
40:13rather subtle.
40:15However, when the
40:16first new variant
40:17cases emerged, the
40:19changes were so
40:20striking, even on
40:21initial examination,
40:22that we were
40:23overwhelmed by the
40:25differences.
40:26spongiform change, as
40:34well as the spongy
40:35change in the
40:36tissue, there were
40:37large numbers of
40:38these plaques, these
40:39aggregates of
40:40prion protein, but it
40:42wasn't just the
40:43plaques, they had a
40:44particular shape, they
40:45were large, they were
40:47rounded, and they
40:48were surrounded by a
40:50ring or a halo of
40:51spongiform change, and I
40:53had never seen anything
40:54like that before.
40:55I think I realized
40:56then that undoubtedly
40:57this was something
40:58different, something
41:00new, something very
41:02disturbing, and
41:03something for which we
41:04had no explanation.
41:06I think we all had to
41:06agree that this was
41:07something unexplainable,
41:10and that we couldn't
41:10just put it down to a
41:14chance occurrence.
41:15By early 1996, ten
41:17cases of the new
41:19variant of CJD had
41:20appeared throughout
41:21Great Britain, all in
41:23young people.
41:25While there was no
41:25hard scientific proof
41:27that mad cow disease
41:28had caused their
41:29deaths, the
41:30circumstantial evidence
41:31was overwhelming.
41:34The news that BSE
41:35might have infected the
41:36human population
41:37shocked the world.
41:44Nations across Europe
41:46ban British cattle and
41:47meat, just as the
41:49United States have done
41:50in 1989.
41:52Fear struck home when
41:54the public learned that
41:55the practice of feeding
41:56cows the rendered remains
41:58of other animals was
41:59still legal in the United
42:01States.
42:02Cows should not be eating
42:03other cows.
42:04It has just stopped me
42:06cold from eating another
42:07burger.
42:09While British beef was
42:11still for sale, some
42:13restaurants and fast food
42:14chains throughout England
42:16removed it from their
42:17menus.
42:18But was mad cow disease
42:20really the cause of the
42:22new disease?
42:24The timing of these
42:26cases is possibly of some
42:29importance and the
42:31reason for that is that
42:32if the population of the
42:34UK were exposed to the
42:36BSE agent in the mid-1980s,
42:38it would not be unexpected
42:41if there were a link that
42:42cases would start to occur
42:43in the mid-1990s.
42:47The striking similarity in
42:49both the clinical features
42:51and the pathology in these
42:52cases suggests that a
42:53common agent is operating
42:55and this, I think, points
42:58towards BSE as the most
43:00likely cause.
43:02I think the most likely
43:03explanation is that these
43:04cases have occurred
43:06because of BSE.
43:09If these ten people have
43:10died from BSE, then
43:14essentially the entire
43:15population of Britain is
43:16at risk.
43:18But with so few cases,
43:21scientists could not
43:22accurately predict the
43:23extent to which the human
43:24population would be
43:25affected.
43:29In the first year of the
43:30cattle epidemic, only ten
43:32cows fell ill.
43:35Eventually, the death toll
43:36exceeded 170,000 cows.
43:42Would the human epidemic
43:43follow the same course?
43:47One of the main questions
43:49we have to address now is
43:51why only this small group
43:55of patients has developed
43:56this disease.
43:57If you believe that this is
43:59BSE, then potentially millions
44:01of us in Britain have been
44:02exposed to the agent in the
44:05food chain.
44:06So what is special, what is
44:08different about these people
44:10that, in a way, allowed them
44:12to develop the disease?
44:14One of the only clues so far
44:17has been found in the
44:18genetics of those who fell
44:19ill.
44:21There is some evidence from
44:22CJD that people of a
44:25particular genetic makeup are
44:28particularly susceptible to
44:29CJD.
44:30The gene responsible for the
44:32prion protein seems also to
44:34affect our susceptibility to
44:36prion diseases.
44:38Along this gene, DNA codes for
44:41two different types of amino
44:42acids, methionine and valine.
44:46A person whose DNA codes for
44:48one methionine and one valine
44:50seems less susceptible to
44:52prion diseases.
44:54Someone who has two valines is
44:56more vulnerable.
44:57And those who have two
44:58methionines are called
45:00methionine homozygotes and
45:03seem to be the most susceptible
45:05to the new kind of CJD.
45:09The first two published cases
45:11were known to be methionine
45:12homozygotes.
45:14And earlier this year we began
45:15to get the results back on the
45:17other new variant cases.
45:18And this established that there
45:20was a link between them and
45:21that was that they were all
45:22methionine homozygotes.
45:23All ten of the new variant CJD cases
45:27bore this genetic trait, but this
45:29offers little comfort.
45:30Looking at the distribution of
45:32methionine homozygotes in the
45:34United Kingdom population, it's not
45:37really all that reassuring because
45:39about 18 million people in Britain
45:41are probably methionine homozygotes.
45:46Testing so many people is out of the
45:48question.
45:51And scientists are unsure just how
45:54much one genetic type confers
45:56protection or vulnerability.
46:01In addition, there are still many
46:04other mysteries about the risk BSE
46:06presents to humans.
46:09It's very hard to try and perform
46:10any sort of real risk assessment
46:12as to what the outcome of this
46:16might be, how many people might get
46:18infected, what sort of exposure
46:20might be a risk.
46:22We really know so little, in fact
46:25none really, of the key
46:26ingredients that you'd need to know
46:27to make a risk assessment.
46:29For example, no one knows how many
46:32British cows contracted BSE or how
46:36many entered the food chain.
46:41Complicating risk assessments even
46:43further is the mystery of how much
46:45infected material a human being would
46:48have to eat to trigger disease.
46:52Using a herd of test cattle, the
46:54British government has established a
46:56minimum dose fatal to a cow.
47:02Eating just one quarter of a teaspoon
47:04of BSE-infected brain is enough to kill it.
47:08It takes a much larger dose to pass infection
47:18from one species to another than within
47:21the same species.
47:24No one knows exactly how much or whether
47:28seemingly insignificant amounts of BSE can
47:31accumulate in the body until they reach a
47:34fatal level.
47:36We don't know yet whether there's a
47:38cumulative dose effect.
47:39We know in animal models that there's a
47:42minimum dose that you have to give to
47:44produce the disease.
47:46We don't know yet if you divide that dose up
47:49into small portions and give it over a long
47:51period of time, whether it would also be
47:53effective.
47:54And this is an important issue with respect to
47:56BSE in humans.
47:58It may be that you have to have a very large
47:59exposure to BSE over a short period of
48:02time to get the disease.
48:03It may be that small amounts over years
48:05could build up to produce the disease.
48:07And we really don't know the answer to that
48:08question.
48:09But there's likely to be some cumulative
48:11element to it simply because the
48:13infectious agent itself is so persistent in
48:16the body it can stay there for a long
48:17period of time.
48:18So it's bound to build up to some extent.
48:21In addition, experts have not determined
48:23whether BSE exists throughout an infected
48:26animal's body or just in the brain and
48:29spinal cord where it accumulates.
48:32Flesh, muscle, milk and blood have never
48:35been found to be infectious, although these
48:37tests are not definitive.
48:41But the greatest mystery is how easily BSE can
48:44cross the species barrier from cows to
48:47humans.
48:48A strong species barrier would protect most
48:51people, but a weak one would leave a
48:53many more susceptible.
48:56The species barrier between cows and
48:57humans was unknown.
48:59You can't just assume that it's going to be
49:00an absolute one.
49:02Of course, we can't measure it because that
49:04would involve injecting humans with BSE,
49:06which clearly we wouldn't do.
49:11Scientists need to know more about what
49:13controls the species barrier.
49:16And the only way to find out is to do the
49:18experiments.
49:19You can't just sit down with a piece of
49:21paper and work out how easy it will go from one
49:23species to another.
49:24It's something you have to determine
49:26experimentally.
49:30One of those experiments focuses on how the
49:33species barrier works on a molecular level.
49:36evidence from other labs has suggested that the type of
49:40PRP protein that an animal makes can determine whether or
49:46not that animal is going to be susceptible to infection with
49:50the agent from a different species.
49:52So what we know is that this protein, this PRP protein,
49:55is composed of a sequence of what are called amino acids,
49:59which are linked in a long chain.
50:00And that the amino acid sequence of PRP from an animal like a
50:05sheep differs from the sequence in an animal such as a cow.
50:10And what we're interested in determining is if it's those
50:13differences between these two types of PRP that can affect
50:18whether or not this species barrier is broken and infection can
50:22occur.
50:22Preola is investigating how scrapie is passed between two closely
50:28related animals, hamsters and mice.
50:33Curiously, mice can't be infected with hamster scrapie.
50:37But hamsters can be infected with mouse scrapie.
50:42To understand why, Preola analyzed the differences in their PRP
50:47proteins.
50:48Between the mouse PRP and the hamster PRP,
50:52there are 16 amino acid differences.
50:56And what we were able to do is show that you can control
50:59formation of this protein by changing just one amino acid.
51:03So one change out of 254 amino acids could be enough to allow the
51:10formation of this abnormal protein.
51:13If you get the formation of this abnormal protein,
51:16you're probably going to get disease.
51:18One of the things that this piece of work implies is that very minor
51:24changes in the PRP proteins between two different species could really
51:29have a dramatic effect on whether or not you get formation of this
51:33abnormal protein.
51:34This work indicates that the species barrier against BSE can be breached fairly easily, which would seem
51:43to have grave implications for humans.
51:48Experiment after experiment is confirming that this is already happening, leaving little doubt
51:54that new variant CJD is in fact the human form of mad cow disease.
52:00To date, it has killed more than 20 British people.
52:03So far, the United States has been lucky.
52:07No cases of BSE or new variant CJD have ever been found here.
52:13But can it remain that way?
52:15I think the likelihood of BSE existing in this country is small.
52:21It's not zero, but it's small.
52:24And I think the phenomenon that BSE is widespread in this country is simply not true.
52:33To prevent BSE spreading in the food chain, the United States government has at last banned the practice
52:40of feeding most, although not all, animal remains to cows and sheep.
52:45Thanks to similar measures in England, BSE is now on the decrease there and may even be eradicated
52:55from British cattle herds early in the next century.
52:59But it remains to be seen what direction the human disease will take.
53:05It's far, far too early to say what sort of epidemic that's going to be, whether it's
53:08just going to be 20 or 30 cases over several years or whether it's going to be hundreds
53:15or potentially thousands of cases.
53:16We have to wait and see.
53:18If the two dozen odd cases of CJD in Great Britain are most of the cases that we will
53:28ever see, that is to say, if what has happened basically represents a few susceptible people,
53:36then I think even if BSE existed in this country, it would not be especially panic producing.
53:42If on the other hand, within two or three years, we start to see hundreds or thousands
53:48of cases of CJD in humans in Great Britain, then that's going to be cause for concern all
53:54over the world.
54:07Are prions behind this dreaded disease?
54:10Do they even exist?
54:12For all the raging debate, log on to NOVA's website at www.pbs.org.
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