NOVA examines the complex world of parasites, parasitic diseases and the exciting work currently being done by a new breed of medical researchers as they meet the challenge of conquering the world's number one medical problem.
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00:00We're in on what is virtually a revolution in scientific ideas and scientific development.
00:16We wake up every morning looking for what's going to happen next.
00:22It's a revolution to overpower the world's devastating parasitic diseases.
00:26Diseases which blind, cripple, weaken, and kill.
00:32One million African children will die this year from malaria, but their prospects may
00:36soon be dramatically transformed.
00:37I think the progress that has been made in the past five years towards making a malaria
00:43vaccine, and five, six, eight, progress that has been made in the preceding 50 years.
00:48But will the scientific progress against malaria and the other parasitic diseases reach the
00:53people who suffer?
00:55When can we expect man's ultimate conquest of the parasites?
01:04Major funding for NOVA is provided by this station and other public television stations
01:08nationwide.
01:11Additional funding was provided by the Johnson & Johnson family of companies supplying health
01:15care products worldwide.
01:21And Allied Corporation, an advanced technology company proud to support outstanding science
01:25programming on public television.
01:49One of the excitements about the field of the biology of parasites is that it's rare
01:54that one finds a field where at the same time one has such excitement in the basic biology
02:01of organisms and where one's work has almost immediate direct relevance to solving some
02:08very major health issues in the world.
02:14These are all parasites.
02:16Organisms responsible for a multitude of human diseases.
02:29They are complex creatures, extraordinarily clever at invading our bodies and evading
02:34our defenses.
02:39Parasites' complicated life cycles make them scientifically intriguing, but medically
02:44challenging and deadly.
02:49The parasites of the tropics cause a devastating group of diseases.
02:53River blindness, filariasis, philharzia or schistosomiasis,
03:14and malaria.
03:17These diseases are the targets of a new scientific assault.
03:27The victims of parasitic disease live principally in the poor developing areas of the world.
03:36Illness seems the inevitable result of substandard living conditions.
03:42And tragically, there is often an insidious cycle of disease and poverty.
03:49For some of the diseases, certainly if poverty could be eliminated, one could find easier
03:56solutions to them.
03:58But many of them are the things we're talking about, like philharzia, things like African
04:04sleeping sickness, like river blindness.
04:08These things are very closely bound to the tropical environment.
04:12And rather than just being due to poverty, they themselves in fact tend to aggravate
04:18poverty.
04:21Eliminating disease could break the cycle and overcome critical barriers to economic
04:25development.
04:27This is the hope which drew scientists from around the world here to the Marine Biological
04:31Laboratory in Woods Hole, Massachusetts.
04:36Gathered together for a conference by the Rockefeller Foundation, these researchers
04:40have spent the last five days planning new weapons against the parasite invaders.
04:46They are committed to conquering the diseases these invaders cause, the so-called great
04:50neglected diseases of mankind.
04:55Well the great neglected diseases are called great because they're problems of usually
05:01hundreds of millions of people.
05:04Hundreds of millions.
05:06And they're called neglected because they're neglected by the scientific establishment
05:10of the world.
05:13And neglected by the funding agency of the world.
05:15And neglected by the political establishments of the world.
05:22But the work of these scientists could spell the end of that neglect.
05:27We've gone to the best laboratories in the world, regardless of where they are in the
05:32developing world.
05:33And we found there are a lot of scientists, outstanding scientists, sitting around who
05:37really are closet altruists.
05:40If they were given the opportunity to work on the great neglected diseases where they
05:45saw an enormous opportunity not only to deal with problems of vast numbers of people, but
05:51an opportunity that's been lying fallow for very many years, about which they could really
05:54do something, they jumped at the chance.
05:58And the targets of their research are formidable creatures.
06:02Parasites are more complex by far than viruses and bacteria.
06:06They range all the way from microscopic single-celled organisms to worms.
06:16Parasites cannot survive on their own.
06:18To live, they must invade the body of another.
06:22From that host, they take food and shelter.
06:25In return, they give nothing.
06:28Because they depend upon their human hosts, parasites must not kill before their own life
06:33cycles are complete.
06:35The diseases they cause, therefore, are usually chronic, long-term, and debilitating.
06:42The most common parasites are intestinal worms.
06:47One-third of the world's population are infected with Ascaris worms, tapeworms, or worst of
06:58all, hookworm.
07:02One billion people have hookworm.
07:05Inside the body, they cling to the walls of the intestines with sharp, cutting teeth.
07:11They live on human blood and cause a chronic, debilitating anemia.
07:20Not all parasites, however, are so particular about where they live.
07:24In West Africa, there is a worm, the guinea worm, that will live almost anywhere in the
07:29body.
07:32The worms, which grow up to three feet long, often emerge as sores in the skin.
07:40The only thing to do is pull them out.
07:49These kinds of parasites, guinea worm, Ascaris, hookworm, thrive in conditions like these.
07:57The parasite infects the host at water holes or from the soil, and then after growing in
08:03the host, passes back through defecation or other means to the environment, where it waits
08:09to begin the cycle again.
08:17But parasites like these can and have been eliminated with improved sanitation, effective
08:22hygiene, and clean water.
08:25It's the next class of parasites which has really defeated our efforts at control.
08:30These parasites have expanded their life cycles to include another creature besides man, a
08:36carrier, or vector, usually a blood-sucking insect.
08:41This vector carries the parasites from host to host as it bites them.
08:49No matter how hygienically you live, you can't stop insects biting.
09:01Therefore, vector-borne diseases among them affect hundreds of millions of people.
09:14One group is caused by the filarial worms.
09:16Well, the filarial worms are roundworms, all of them transmitted by blood-sucking insects.
09:22Now, there are two of major importance for human welfare.
09:27One is the lymphatic-dwelling parasite, got a terrible name, Boucheria bancrofti, which
09:33affects about 300 million people, mainly in the hot, humid, tropical areas of the world.
09:42The disease is manifested by elephantiasis, the big leg, fever, filarial fever, mainly
09:51people in Southeast Asia.
09:56The other filarial parasite, which in some ways is the most dreadful of all the human
10:01parasitic diseases, is onchocerciasis, or river blindness, and a lot of the parasites
10:08get into the eye and it causes blindness.
10:14There are some areas in West Africa where 30% of the total adult population are blind
10:22due to this parasite.
10:35This is the filarial worm that causes river blindness.
10:40The insect vector which carries it is a simulium fly.
10:45When squashed, you can actually see the parasite moving in the abdomen of the insect.
10:50A few such parasites won't harm the fly, but when they're injected into man, the effect
10:55is devastating.
10:58Inside the human body, worms collect together in hard nodules under the skin.
11:03Deep within the nodules, the females start to produce millions of offspring, microfilaria,
11:08which are released continuously into the tissues.
11:12When these baby worms start to die, after about two years, they trigger a massive reaction,
11:18a terrible itching in the skin, which has driven some victims to commit suicide.
11:25In the eyes, they cause soreness and eventually blindness.
11:34In Africa, this disease only occurs in communities that are located near fast-flowing rivers
11:40because that's where the simulium fly breeds, hence the name river blindness.
11:54Now that disease can only be controlled either by killing the vector in the running water
12:00with insecticides, and this is a formidable problem in a country like Africa.
12:09There's a World Bank program there, bombing all the rivers of West Africa with insecticides.
12:16Unfortunately, the fly developed resistance to the best insecticide available, and the
12:21local governments have been forced to use alternative, more expensive materials.
12:28Now you say, well, why not get rid of this disease by treating the people, because they're
12:32already badly afflicted.
12:35Unfortunately, the disease is caused by the dying parasites.
12:39In the natural course of the disease, the parasites die in the skin or in the eye, and
12:45they cause the disease.
12:46So if you treat the people and kill the parasites, you often make the disease worse.
12:53The schistosome parasite causes bilharzia, or schistosomiasis.
12:58More than 200 million people in tropical areas throughout the world have it.
13:04The worm gains access to man from the water.
13:12It literally burrows through the skin.
13:17Once inside, the parasites grow, moving freely in the veins of the liver or bladder, where
13:23they live and mate for seven to ten years.
13:33The victim's problems begin when the females start laying eggs, hundreds a day.
13:40These eggs travel through the walls of the liver or bladder.
13:47Then the body's own attempts to fight off disease produce inflammation, which destroys
13:52these organs.
13:56Blood flow to the liver may eventually be restricted, causing the telltale swollen belly
14:01of chronic bilharzia.
14:05The bilharzia parasite comes from the water, and so to survive it must return there.
14:13When people excrete near water, the eggs find their way back.
14:19The parasites hatch out and swim off to find another host in which to complete their life
14:26cycle.
14:28In this case, the host is not an insect, but a water snail.
14:38Inside the snail, the parasites multiply, and finally they emerge back into the water
14:44as baby worms.
14:56Then they're ready to begin the cycle again by infecting new human hosts.
15:07It is a terrible disease because it reduces the survival of man.
15:12A lot of people in the endemic areas die at a young age with chronic complications, which
15:18even include things like cancer of the bladder as a complication of the bladder bilharzia,
15:24and terrible disease of the liver for both the Schistosoma japonica and the other one,
15:29Schistosoma mansinae, that affect the liver.
15:32So it's a very, very chronic disease.
15:36It's been very difficult to control, and I say that snails are not easy to kill because
15:43they have an enormous biotic potential.
15:45If you leave one or two snails in the water, within a few months they're back to the same
15:50numbers that they were before you added the molluscicide, and you have to add this molluscicide,
15:56the thing that kills the snails, forever.
15:58You have to keep doing it forever if you want to control the snails.
16:05And the snail's watery habitat is being daily extended by third world development projects,
16:11dams for hydroelectricity and irrigated farming.
16:15Tragically, modernization intended to raise people's standard of living and increase food
16:20supplies is simultaneously spreading disease.
16:24To control the parasite in man, we now have one or two very, very good drugs,
16:29but you have to treat the whole population.
16:32And this is almost impossible in the areas where the disease occurs,
16:37because they are in the most underdeveloped countries of the world.
16:46Not all the parasites, however, are worms.
16:49Some are single-celled organisms like the trypanosome that causes sleeping sickness.
16:56While this disease debilitates thousands of Africans, its main effect is on cattle.
17:02Africa could be one of the largest meat-producing regions in the world.
17:06The conditions are ideal, but for the trypanosome and its vector, the tsetse fly.
17:15The tsetse has a voracious appetite.
17:17It can drink its own weight in blood in seconds.
17:25Since the parasite depends on the insect,
17:28one obvious approach is to destroy the tsetse fly with insecticides.
17:37And throughout Africa, the only place where tsetse flies live, it's been tried.
17:42But the areas are simply too vast.
17:45Vector control programs have been very expensive and have had only marginal success.
17:50In some areas, they failed completely.
17:56It's very difficult to control them in the great savannah belts,
17:59because the tsetse fly not only feeds on man, but feeds on game animals.
18:06While these animals do not have the ability to survive in the wild,
18:10while these animals don't actually get sleeping sickness,
18:13they carry the parasite in their blood, forming a huge reservoir of trypanosomes.
18:21That one is going to be impossible to get rid of,
18:23unless you get rid of the game animals, which would be rather unpopular.
18:31Filariasis, bilharzia, and sleeping sickness affect millions.
18:37But malaria is the single most important parasitic disease,
18:42because it is the most ruthless killer.
18:45More than two million deaths a year worldwide.
18:52The parasite infects man from a blood-sucking mosquito.
18:55And once established in the host,
18:58this single-celled organism invades the red blood cells and destroys them.
19:07Malaria is the great killing disease of mankind in the tropics.
19:13It is the most formidable tropical disease.
19:17There are probably a thousand million people living in areas
19:22where anopheles mosquitoes are transmitting the most dangerous type of malaria.
19:27There are several different types of malaria.
19:30One which is an acute, malignant malaria,
19:33and there are others that are chronic, relapsing-type malaria.
19:36All of them transmitted by anopheles mosquitoes.
19:40A very, very wide range of anopheles mosquitoes.
19:43Hundreds of different species, each with its own different habitat.
19:48Very difficult to control in the environment.
19:52But most of them, fortunately, rest in houses at night
19:57after they've been biting the people.
20:00And so you can control malaria by using insecticides sprayed inside the houses.
20:05Spraying with insecticides has broken the chain of malaria transmission in some areas.
20:11The possibility that insecticides might allow us to eradicate malaria everywhere
20:16was the World Health Organization's great hope in the 1950s.
20:21The attack on malaria is the primary objective.
20:27Once all the facts are assembled, the attack can begin.
20:31This is a kind of commando assault on the area.
20:36Many hands are recruited.
20:38Each day, armed with their weapons of sprayers and DDT, they attack another village.
20:46The inside walls of all the houses are sprayed.
20:49The teams remove all the personal effects from walls
20:52so that every square inch of surface can receive an adequate quantity of insecticide.
20:57Marking the date on the walls of houses is for the information of the spraying teams
21:02when they come around to renew the insecticide.
21:05After World War II, there was a euphoria about the possibility of eradicating malaria
21:10for two reasons.
21:12There was DDT that killed mosquitoes,
21:15and there was chloroquine that killed the malaria parasite.
21:19And there was an eradication scheme to eradicate malaria
21:24And there was an eradication scheme was devised,
21:28and everybody thought, well, that was going to be it.
21:32And by the early 60s, actually, malaria had been eradicated in the southern United States,
21:38around the Mediterranean, and markedly decreased in Asia.
21:42Sri Lanka was the Asian nation which chalked up the most impressive results.
21:47From well over one million cases, malaria declined steadily
21:51until in 1963, there were only 18.
21:55But after initial success, there were several years of epidemic outbreaks.
22:00Control efforts have never regained the upper hand,
22:03and today the numbers are again increasing rapidly.
22:08Eradication euphoria was vanquished by the wiliness of the malaria vector.
22:13Throughout the world, Anopheles mosquitoes were becoming resistant to DDT.
22:21For malaria victims, the picture is bleaker still.
22:25Simultaneously, the parasite evolved resistance to the drugs for treating the disease.
22:32Over the years, there's been a dramatic increase in malaria,
22:36partly due to the fact that mosquitoes have become resistant to DDT and other insecticides,
22:42and partly to the fact that the parasite has become resistant to first chloroquine,
22:49and now more and more of the new, of the other malaria, drugs against malaria.
22:54And also because it's so expensive to keep a control program going,
22:58and when you only have a few cases,
23:00governments are reluctant to spend the millions to do this.
23:04Malaria maintains its grip on the tropics,
23:07and in virtually all these areas, the vector mosquitoes are resistant to DDT,
23:12and often to other pesticides as well.
23:14Drug-resistant parasites have appeared throughout South America,
23:18East Africa, and Southeast Asia, where the problem is now a medical crisis.
23:26In parts of Thailand, the organism is resistant to every known drug.
23:31So you take the risk of going into these areas and developing
23:34a potentially fatal case of malaria, and have no way of even treating it.
23:39So we see it as a dreadful problem out of control.
23:41We used to control it with insecticides, but the insects,
23:44the mosquitoes that transmit malaria, have become resistant to the insecticides.
23:48So what do we do?
23:53Our attempts to control malaria have only made the parasite more deadly.
24:00But there is another way of dealing with disease,
24:03one that doesn't require insecticides or drugs.
24:07Vaccination is the only way.
24:09For some diseases caused by viruses and bacteria, it's been a great success story.
24:23You won't see this disease, smallpox, anywhere in the world now, thanks to vaccination.
24:30By 1979, the World Health Organization could announce its total elimination.
24:34Smallpox is caused by a virus.
24:37If we could vaccinate against diseases caused by parasites,
24:41perhaps we could control them as well.
24:44It needs the least cooperation of the population that you're trying to treat.
24:50If you can vaccinate them when they're babies, and they're going to be then protected, that's great.
24:55If you're going to treat them with drugs, you've got to find them,
24:58you've got to get them to come to you.
25:00If you're going to treat them with drugs, you've got to find them,
25:03you've got to get them to come to the clinic,
25:05in some cases to go to hospital, in order to have these drugs.
25:10Vaccines rely on the workings of the body's own defences, the immune system.
25:17Every invading organism displays its own unique pattern of surface molecules called antigens.
25:23These antigens are too small to be identified, even with the most powerful electron microscope.
25:34But the immune system can recognize them.
25:40And if it does so in time, it can send large antibody molecules to stick to them.
25:46The invaders get surrounded with gluey molecules,
25:50and then the body's killer cells come in and finish them off.
25:56During a successful bout with an infectious disease,
26:00the human bloodstream grows filled with antibodies.
26:05Afterwards, they remain behind, prepared to fight off any new invasion.
26:10The person is not infected, but the body is.
26:12Prepared to fight off any new invasion, the person is now immune to the disease.
26:18A vaccine activates the body's defences without actually causing an illness.
26:24Infectious organisms are pumped into people, but in a safe form, either weakened or dead.
26:30Just as with an actual disease, antibodies and immune cells are produced, and immunity develops.
26:37The principle has worked for viruses and bacteria,
26:40but so far there is no vaccine against a human parasite.
26:44Yet scientists agree the best chance is against the most deadly, malaria.
26:49I think first of all, children do recover from malaria, so there is a good ongoing immune response.
26:58Secondly, I think malaria is probably the worst parasite at evading immune responses,
27:04so I think it's a better target.
27:07But a difficult target nevertheless, for malaria has a complex life cycle.
27:12The disease begins when an infected mosquito bites,
27:15injecting the single-celled parasite in its sporozoite stage.
27:21These sporozoites travel to the liver, where they multiply and emerge in a new form,
27:26merozoites.
27:28The merozoites start a cycle invading red blood cells,
27:31multiplying and bursting out to infect new blood cells.
27:34The victim experiences fever and chills.
27:38Some merozoites become gametocytes,
27:40which are ingested by a mosquito who bites the malaria victim.
27:44Inside the mosquito, they produce sporozoites,
27:47capable of infecting another human when the mosquito bites again.
27:51Well, the situation here is very interesting,
27:54and a good illustration of the life cycle complexity of a parasite.
27:59Malaria goes in as the sporozoite, from the mosquito goes to the liver,
28:04escapes from the liver into the blood,
28:05multiplies, and then is taken back by the mosquito to perpetuate the cycle.
28:10And malaria vaccinologists, if you like, are focusing on these three stages
28:17of the sporozoite, which is being introduced,
28:19so anti-infection immunity or vaccination,
28:23the stage in the blood, which gives you the disease symptoms of malaria,
28:27anti-disease stage of vaccine,
28:30and then the transmission, the stage which is transmitted,
28:34the gametes through the mosquito, anti-transmission immunity.
28:38And in laboratories around the world,
28:40researchers are looking for the malaria parasite antigens,
28:43which might induce these different kinds of immunity.
28:47They're employing the newest techniques of molecular biology,
28:50and they're learning how devious parasites can be.
28:53Among the dozens of molecules on the parasite's surface,
28:56surface antigen molecules, only some trigger the body's defence.
29:02The parasite is a mosaic of antigens, many hundreds of antigens,
29:07which are inducing immune responses,
29:09most of which are totally useless, if not harmful,
29:12some of which we know are useful and spectacularly successful
29:17in eliminating the parasite from certain individuals, at least.
29:21Now, if we can identify those molecules, that small subset of molecules,
29:26that should form the basis of the molecular vaccine.
29:30Most scientists are working on the disease-causing merozoite stage.
29:34After early successes, however, they've run into trouble.
29:38Experimental vaccines, which were being tested in monkeys,
29:41only seem to work if mixed with a toxic additive unacceptable in man.
29:48The major breakthrough has come in work on the first infective sporozoite stage.
29:52After 20 years of painstaking research, a team at the NYU Medical Center
29:56believe they have identified parasite surface molecules
30:00which will prepare the human immune system to fight off sporozoites.
30:04Leaders of that team, Victor and Ruth Nussensweig.
30:07The role of our immune system is to recognise those same molecules
30:13which are important for the parasite and neutralise them.
30:17But this is not always very easy to do,
30:19but this is not always very easy to do
30:21because the parasite has a lot of bag of tricks to fool this immune response.
30:27So what is the role of the scientist?
30:29The role of the scientist is to find out what are these molecules
30:33and then to produce or find methods of producing large amounts of these molecules
30:39and then these molecules can be eventually used as vaccines.
30:43The hope is that vaccinated humans will produce antibodies
30:46that prevent the sporozoite from entering a liver cell.
30:53But the sporozoite finds its way to the liver in only 30 minutes,
30:56so that immune response must be rapid.
31:01If just one sporozoite escapes, a person will get malaria.
31:08Many scientists doubted that a vaccine could ever work.
31:11When we started our research approximately 20 years ago on a malaria vaccine,
31:19the development of such a vaccine appeared to be a very difficult task.
31:25In order to obtain sporozoites for the research,
31:30it was necessary to breed large number of mosquitoes in the laboratory,
31:36infect these mosquitoes on animals or men,
31:42dissect these mosquitoes one by one to obtain the salivary glands
31:47where the parasites are located,
31:50and end up with a rather small number of parasites for experimental purposes.
31:57We did a large number of experiments with mice and rats
32:03using irradiated sporozoites as a vaccine.
32:09The irradiation left the sporozoites incapable of causing malaria,
32:13although they still displayed the parasite's key surface antigens.
32:24Next, the mice which had received injections and an untreated control group
32:28were challenged with live infective parasites.
32:31Of the 149 untreated mice, 145 died.
32:37Of the 147 vaccinated mice, only 23 died.
32:43These mass results were confirmed in similar experiments on rats,
32:46monkeys, and a small group of human volunteers.
32:51Next, the Nussenzweigs took serum containing all the antibodies
32:55the vaccinated animals produced and added it to live sporozoites.
33:00Under the microscope, they observed a striking response.
33:04The surface of a normal sporozoite is smooth,
33:07but after the addition of immune serum, a rough coat develops,
33:10and eventually a tail-like precipitate grows.
33:14These sporozoites were no longer infective,
33:17so the reaction called the circumsporozoite or CSP reaction
33:21was a sign the crucial protective antibody was present
33:24and reacting with the parasite's key surface.
33:30The next task was to isolate this key surface antigen.
33:34To do this, members of the Nussenzweig's team relied upon a powerful new technique
33:38to produce large quantities of very pure antibodies known as monoclonal antibodies.
33:44Amid the many different monoclonal antibodies they made,
33:47the Nussenzweigs hoped to find one that matched the malaria parasite's key surface antigen.
33:52We knew that the important substance was on the parasite's surface,
33:57so all we had to do was develop monoclonal antibodies
34:01against the surface of the parasite and choose the right one,
34:05and very soon we found the right one.
34:07How did we know that it was the right one?
34:09Simply because when we mixed that monoclonal antibody with the parasite,
34:16we found that CSP reaction in which the parasite was reacting
34:20CSP reaction in which the parasite looks like he's trying to get rid of that antibody
34:26and makes that long, long tail.
34:29So that monoclonal antibody was binding to precisely the molecule which we're looking for.
34:38This methodology of monoclonal antibodies,
34:43in addition to the methodologies of recombinant DNA,
34:50made the advances much more rapid, much more than we could ever predict,
34:59so that within a relative short period we were able to do the experiments to develop a vaccine.
35:08The vaccine was to be made up solely of the key malaria surface antigen,
35:12and in order to mass produce that antigen,
35:15the Nussenzweig's team employed the techniques of recombinant DNA or genetic engineering.
35:22First, they ground up mosquitoes which were heavily infected with malaria parasites.
35:30Next, the genes were pulled out of the parasite.
35:36The genes all code for different parts of the parasite,
35:39including the single gene which makes the key surface antigen molecule.
35:45But they must all be put into bacteria for cloning
35:48because individual genes are too small to tell apart.
35:56Bacteria are chosen because they can be tricked into accepting parasite genes as their own.
36:03Each of the thousands of different gene fragments are taken up by the bacteria,
36:08and the bacteria are then grown up or cloned,
36:12copying not only their own genes, but the extra parasite genes as well.
36:18The Nussenzweig's prepared hundreds of dishes of bacteria to obtain the gene they were searching for.
36:30Bacteria divide extremely rapidly.
36:33Overnight, each cell will have grown into a colony the size of the head of a pin.
36:38With luck, one of these colonies contains the gene coding for the key surface antigen.
36:44The challenge is to find it among the thousands of colonies without destroying it in the process.
36:50The solution was to make copies of the original colonies.
36:55A paper filter is laid on top of the original,
36:57and a weight applied to both.
37:07The filters are pricked with a pin to provide crucial alignment marks.
37:11This procedure is carried out twice.
37:13The filters are then returned to dishes, and after incubation overnight,
37:17the researcher has two identical copies of the original.
37:21These duplicates are then bathed in a solution to which radioactivity is absorbed.
37:27The solution is then poured into a tube,
37:29and the tube is filled with the solution.
37:33The solution is then poured into a tube,
37:35and the tube is filled with the solution.
37:37These duplicates are then bathed in a solution to which radioactive monoclonal antibody is added.
37:43This monoclonal antibody should stick to the colony making the key surface molecule, and nowhere else.
37:51The filters are bathed for two hours, and then washed to remove any excess antibody.
37:59Next, the dried filters are laid out and covered with a sheet of x-ray film sensitive to radioactivity.
38:07The developed film is then aligned with a set of duplicate filters.
38:14The dark exposed points over the filters mark the sought-after colonies.
38:25Finally, using the pin pricks as a reference,
38:28the scientist matches the black mark on the film with an actual bacterial colony.
38:38Blue dots aligned with pinholes.
38:41The black dot indicates the target colony.
38:45Bacteria from this colony can now be grown to obtain a virtually limitless supply of parasite antigen and its gene.
38:53But when we got the gene corresponding to this protein,
38:57from the gene we could learn about the structure of the protein.
39:01And we learned something very interesting.
39:03We learned that about half of that molecule consists of identical sets of building blocks,
39:11and building blocks which are amino acids.
39:15And since these are very small sets, we can now synthesize them,
39:20and hopefully these can be used also as a vaccine.
39:24In this case, it will be a synthetic vaccine.
39:27It's an interesting discovery.
39:30It's an entirely new idea for a vaccine,
39:32and one which may provide better protection than any natural substance,
39:36because it would be made up solely of molecules that provoke a strong and effective immune response.
39:42And it has been made possible by stunning advances in molecular biology.
39:48The work of the nucleus spines is especially exciting,
39:51and it really shows what wasn't possible just a few years ago,
39:56and it really shows what wasn't possible just a few years ago,
39:59is very possible now.
40:01Indeed, in the earlier years, where Rutherford Nussbaum was trying to find out
40:06about the immunology of sporozoites,
40:08and if one could be immune to them,
40:11it was thought that it would be impossible to have a vaccine,
40:14because you couldn't get enough antigen from sporozoites,
40:17from the millions of mosquitoes you'd need to make one.
40:20And nobody expected the molecular biology to come along.
40:24And just with this, it has now made it not only possible,
40:28but undoubtedly the sporozoite vaccine will be the first malaria vaccine
40:33that is going to be tested in people.
40:36This is the exciting part, where the scientists in the laboratory make some interesting discoveries.
40:41Beyond that, to the point where you have a useful drug or vaccine,
40:46there's a lot of development work to do.
40:49Clinical trials, field evaluations, and so on.
40:53Those are much less glamorous, and yet they are essential.
40:58But traditionally, pharmaceutical companies have been unwilling to undertake this development,
41:03because they don't see a market for drugs against tropical diseases
41:07among the people in the developing world.
41:12There's no profit to be made from tropical diseases.
41:15And this is the reality.
41:19You can make more money from the production of a new tranquilizer,
41:24or something to cure a headache,
41:27than you could make from all of the tropical diseases.
41:31Because the people in the developing countries can't afford to pay for the drugs,
41:35and they won't be able to afford to pay for the vaccines.
41:39So can this cycle of disease and poverty be broken?
41:43Is there an alternative perspective?
41:47I believe that a number of these pharmaceutical companies
41:51recognize their social responsibility.
41:54And I'm hoping that in that spirit,
41:57some of them would, in fact, be prepared to invest
42:01in an area which would not be just solely for the commercial interest,
42:06but as part of their investment in development.
42:10Because in the long run, if the developing countries prosper,
42:15that's much bigger markets for them.
42:18If we have the vaccine, we manufacture the vaccine,
42:21we can supply it to the people in the field.
42:23It doesn't mean to say that it's going to work.
42:26We already have probably one of the best vaccines known to man,
42:29the polio vaccine.
42:31If you go to Africa, you'll see plenty of cases of polio.
42:34We have a measles vaccine.
42:36Measles is one of the great killing diseases of Africa.
42:39People have over and over again said,
42:41why are you doing research to develop new vaccines
42:44when we're not applying the vaccines that we have available at the present time?
42:47Well, I'm very pleased to say that there's been a major change
42:51in global strategy for dealing with the diseases of the developing world.
42:54There are movements afoot right now through UNICEF
42:57and through a new organization called the Task Force for Child Survival
43:01to immunize all the children of the world at the present time
43:04and to develop an infrastructure for continuing immunization.
43:07This makes scientists like me exceedingly happy
43:11because what we can say is now you're applying these vaccines,
43:15how can you say we shouldn't produce new vaccines for dealing with problems
43:18like malaria and diarrheal diseases and amoebiasis and African sleeping sickness?
43:22So what it does is it gives us the opportunity to go ahead full speed
43:27and produce the new vaccines and plug them in to the system as it's developing.
43:32The problem is that other anti-parasite vaccines may not be so straightforward
43:38since parasites are capable of some clever immunological tricks.
43:42The bilharzia parasite is one example.
43:46After it penetrates the body, it can live in the veins for up to 10 years
43:50without being rejected.
43:52How does it manage to conceal itself from the body's immune response?
43:56One widely accepted view is that it's able to disguise itself.
44:00Somehow it manages to coat its surface with protein from the host.
44:06Within three days, it's covered up its surface antigens from the body's immune system.
44:11It's disappeared.
44:13The body can't see it, so it can't reject it.
44:19Any vaccine against bilharzia, therefore,
44:22would have to work before this camouflage was complete.
44:28The African trypanosome has an even more clever strategy.
44:32Amazing as it may seem, it's able to vary its surface antigens to evade capture.
44:45As the body recognises the surface antigen and sends antibody molecules to cover them,
44:50so the parasite population is able to change its antigens.
44:56And so the immune response is left floundering, say, one week behind.
45:01By the time the immune response has sort of gathered its resources
45:05to attack a wave of parasites in the circulation,
45:08the parasite has evolved and has changed itself subtly,
45:12so the immune response is left floundering, having dealt with the one wave
45:16and now having to mobilise its resources again to catch up with the next wave.
45:20So that is what we would call antigenic variation.
45:25With such tricks, what chance is there of a vaccine?
45:30Trypanosomes with their ever-shifting antigens,
45:33I don't think there would ever be a conventional vaccine.
45:36You might invent a drug which would stop them changing,
45:39and then the immune response could easily kill them.
45:42Schistosomes, intermediate.
45:44This disguise is a problem because you've only got a limited time, perhaps,
45:48in which to kill the parasite.
45:50But again, you might invent a drug which would work together with the immune response
45:55and perhaps catch them that way.
45:59What about the other parasites?
46:01They also have ingenious mechanisms to evade the immune response.
46:06The Leishmania parasite actually hides inside the very white blood cells
46:11that set out to destroy them, the macrophages.
46:16By some means unknown to science, it enters a hiding place
46:20where the rest of the body's immune system would never think of looking.
46:24Other parasites produce products which are anti-inflammatory.
46:28They sort of suppress the expression of immune responses,
46:31or they cut antibodies in half.
46:33One very effective means is to produce molecules, enzymes,
46:37which cut the main effective arm of the immune response in half.
46:43So any antibody which is crazy enough to bind to the parasite
46:46finds itself cut in half or split up into little pieces
46:49by the enzyme liberated by that parasite.
46:52So obviously a very effective way of neutralizing
46:55one of the major arms of the host protective immune response.
47:00How are parasites able to do these remarkable things?
47:03I think they've learnt to do it.
47:05They've learnt to do it in the hard school of evolution
47:08and they've become very good immunologists.
47:10They have developed ways of evading the immune response,
47:15many different ways and some extremely elegant ways.
47:19Those who have succeeded in evading the host immunity
47:23are the parasites we see.
47:25Those who haven't have been long extinct.
47:29It's a very, very hard school.
47:31I'm quite certain if immunologists had to work in a school as hard as this,
47:36there wouldn't be so many of them as there presently are.
47:43Attempts to liberate people from the filarial parasites
47:46which cause river blindness must take account of another problem.
47:53Inside the body, the growing parasites go through different stages
47:57displaying different antigens.
47:59The disease is actually caused by people's immune response
48:03to the baby worms or microfilaria the adult worms are producing.
48:08Telling them apart immunologically is very difficult but crucial.
48:13A vaccine against the wrong stage of the parasite
48:16might cause disease, not prevent it.
48:19With little hope for a vaccine, what can these people do?
48:24In some cases, entire village communities have fled,
48:27moving to less fertile high ground where their crops often fail.
48:32The parasite has forced a cruel choice between blindness and starvation.
48:37Survival requires staying in the valleys
48:40and for now, these people's overwhelming need is for a drug to control the disease.
48:46The drugs currently used are toxic and difficult to administer.
48:50But recently, a sophisticated new drug with a novel mode of action was discovered.
48:57Ivermectin was developed for veterinary use
49:00but its striking effectiveness led the manufacturer, Merck Sharpen Dome,
49:04to see if the drug might work against human parasites.
49:07The drug company found an enthusiastic partner
49:10in a special program run by the World Health Organization.
49:13The program focuses on eliminating obstacles
49:16drug manufacturers face in the developing nations.
49:19Quite often, industry is reluctant,
49:22even leaving aside the possibility of commercial gain,
49:26they are reluctant to develop agents for controlling tropical diseases
49:31because after they have the product in hand,
49:35it is a very difficult thing for them to get it evaluated clinically in the endemic areas.
49:42The case of Ivermectin, which is now under trial for treatment of river blindness,
49:49is a good example of the thing we mentioned earlier on,
49:53involving industry in a way that is mutually beneficial.
49:59The special program provided support for clinical trials of Ivermectin in humans,
50:04encouraging Merck Sharpen Dome to pursue development.
50:08One test site, the Lancôme-Buchanan Hospital in Liberia,
50:12where doctors from Case Western Reserve and Johns Hopkins Medical School
50:15studied Ivermectin's effectiveness.
50:17Those volunteering had filarial infections,
50:20but the disease had not yet damaged their vision.
50:23Volunteers were divided into three groups,
50:25and unknown to them or the doctors, they received one of three medications,
50:29Ivermectin, the currently used drug, or a placebo.
50:36For two weeks, their reactions were carefully observed.
50:39They underwent detailed eye exams to monitor the effects of the different drugs.
50:47The number of microfilaria in their skin was precisely recorded
50:51by removing a tiny patch of skin for weighing and examination under the microscope.
51:01Follow-up studies were conducted three and six months later.
51:05Initial results are encouraging. Ivermectin looks to be very effective,
51:10and since it is given in a single oral dose,
51:12people can be treated without bringing them to hospitals.
51:16Well, we're very pleased with the results so far.
51:19The first set of cautious trials in man show that a single dose of the drug
51:26brings about a rapid fall in the number of larvae in the skin of the people
51:32who are infected by this organism.
51:36Unlike the other drugs which we have at present,
51:39we use two other drugs, diethylcarbamazine and suramin,
51:43which provoke violent and, in fact, dangerous side effects.
51:48So far, Ivermectin seems to kill the parasites
51:52without provoking such unpleasant and dangerous side effects.
51:57Ivermectin is not a perfect drug.
51:59While it eliminates microfilaria, it does not kill adult worms,
52:03so people may need to be treated every year.
52:05And, of course, the parasite may evolve resistance.
52:10But for this family, Ivermectin could make a world of difference.
52:14This 11-year-old boy is the last member of his family who can see,
52:18but his watery eyes are a telltale sign that within 10 years,
52:22he too will be blind.
52:25Ivermectin may save his sight and allow him to care for his parents.
52:30Still, in our enthusiasm for a new drug,
52:33it is crucial not to repeat previous mistakes.
52:37In the past, we tended to go into battle against this parasite with one weapon
52:42or, as I say to people, with one bullet in our guns.
52:48We shoot, and if we miss, then the parasite chases us back home.
52:53We have to retreat.
52:55I think on the next occasion, we ought to have a variety of weapons.
53:00We have to go in three directions.
53:04Long-term work on vaccine development.
53:08Relatively short-term, new drugs.
53:11Relatively short-term, new methods of controlling the vectors.
53:15And methods of controlling the vectors have got to be as inventive and as innovative
53:19as the parasites and the vectors are themselves.
53:24Parasites are slowly yielding their secrets,
53:28and science is coming closer to conquering them and their deadly diseases.
53:34The payoff, if we're able to control these diseases, would be enormous.
53:38We not only would improve the health of the people,
53:41we'd improve their ability to be productive,
53:46both in the agricultural sector and in the industrial sector.
53:49We could improve, interestingly enough, the whole population problem.
53:54It's been shown time and time again
53:56that one of the major causes of the overgrowth of population and fertility
54:00is the high infant and child mortality in these countries.
54:03So in one fell swoop, we not only improve health, we improve agriculture,
54:07we improve industry, and we improve the great problem that we have with population overgrowth.
54:13So there is good reason to expect that healthier people can be the source of their own prosperity.
54:19But how quickly will science produce the remedies they need?
54:23I am cautiously optimistic, optimistic in the sense that
54:28I think there's a new spirit of interest among scientists throughout the world,
54:34a new sense of collaboration, because some of the work that has been done
54:39has been done in a way which is different from the way scientists usually work.
54:44We've seen scientists sharing results, sharing materials,
54:48from one laboratory to the other, across barriers of geography, politics, language, and so on.
54:55So on that side, I'm very, very optimistic.
54:58It provides an immense satisfaction to see an area in which very little was known
55:05and very little was hoped for developed to a field
55:10where there is an intensive research effort going on
55:14and where the progress is not stepwise anymore, but leapwise.
55:22Science is just beginning to be applied to this field on the sort of level of the best science.
55:28And so we haven't seen very much yet in the practical outcomes.
55:33But what we know is going on is exceedingly exciting,
55:36because it's like a volcano that's building up to explode.
55:40And the work is going on, and it's getting hotter and hotter,
55:43and the pressure is getting more and more.
55:45And I think that within the next five or ten years,
55:48we're going to see a veritable explosion of new drugs and new vaccines for treating these problems.
56:10Transcription by ESO. Translation by —
56:40Transcription by ESO. Translation by —
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