Pigs Help Danish Researchers In Fight Against Alzheimer’s And Psoriasis

In many ways, pigs resemble humans. So Danish researchers are utilising them in a large-scale project where “model pigs” will provide new insights into human diseases such as Alzheimer’s, atherosclerosis and psoriasis, writes Jan Aagaard in magazine Focus Denmark Nr. 3 2010.

We might not like the thought. But the fact is that pigs resemble humans in more ways than we think. So it makes sense to use pigs when researching into human diseases.

This is the background for a series of spectacular projects jointly initiated by the Danish food industry, the pharmaceutical industry and the research community. The aim is to research into the pig’s genetic makeup and use this knowledge to learn more about both porcine and human diseases.

In the part of the project which concerns human diseases, attempts are being made using gene technology and breeding to create “model pigs” which are particularly predis-posed to diseases that usually only affect humans. These model pigs could then be used by the pharmaceutical industry in the development of new drugs.

Minipigs with gene mutations

Pigs are in many ways more suitable for medical testing than “traditional” research animals such as mice, rats, rabbits, monkeys and dogs. Several of the pig’s organs are very similar to human organs, and the physiology and metabolism of the pig are relatively close to that of humans. At the same time, pigs reproduce well, grow quickly and are easy to handle.

A pig. Photo by www.sxc.hu.

Researchers are therefore using pigs to create models for a number of diseases for which they have failed to create models using smaller animals. American researchers have developed a genetically modified pig model for the hereditary lung disease cystic fibrosis – a disease for which it has not proved possible to develop an animal model using mice, despite numerous attempts. Disease models in pigs have also been established for osteoporosis and diabetes.

In the Danish project, researchers are seeking to develop model pigs for testing drugs and treatments for diseases including arteriosclerosis, psoriasis and, not least, Alzheimer’s.

In the Alzheimer’s and psoriasis projects, use is being made of special “minipigs” whose ancestors are Vietnamese pot-bellied pigs. These pigs, which come from the Danish company Ellegaard Gøttingen Minipigs, are well suited for experimental purposes because of their small size.

Successful cloning and breeding

The project with Alzheimer’s model pigs began in 2005 and after just two years caused a stir when the researchers created the world’s first cloned “Alzheimer’s pigs”. Seven identical pigs came into the world equipped with a gene that in humans produces a hereditary variant of Alzheimer’s disease.

Since then, several of the cloned pigs have become gestant by natural means and have given birth to healthy and viable piglets.

Today there are over 20 transgenic pigs available to the project. Getting the cloned pigs to reproduce naturally was an important milestone, as it would be too expensive and uncertain to base production of model pigs solely on cloning.

Hoping for a breakthrough

The original cloned pigs are now three years old, but the researchers are still waiting for the big breakthrough. Even at two years of age, the pigs have shown no sign of brain changes of the type seen in people around 10 years before they are diagnosed with Alzheimer’s.

“We originally hoped that we would see these changes in the pigs in one to three years, on the assumption that the age of the pigs would correspond to a human age of about 35 years. This is the earliest time that changes can be seen in the brain that progress to the depletion of brain cells in Alzheimer’s patients,” says project leader Dr. Arne Lund Jørgensen of the Department of Human Genetics at Aarhus University.

“How pig age translates into human age is a contentious topic, so for now we need to remain patient. At the same time we are endeavouring to accelerate the disease process, by creating pigs that have not one but two gene mutations that can lead to Alzheimer’s,” says Arne Lund Jørgensen.

Investigations into whether the transgenic pigs are showing preliminary signs of Alzheimer’s take place in several ways. Behavioural tests can show changes in the pigs’ memory, and the Danish researchers have also developed a test that can detect changes in the pigs’ sense of smell. The tests are performed while the animals live a fairly normal pig life in the stall.

In addition regular scans of the pigs’ brains are carried out and, once a year, one of the pigs is slaughtered and its brain studied using microscopy. As this article was being prepared, the researchers were planning to slaughter and analyse a 3 year old pig.

Valuable project

“We hope to see changes in this pig’s brain, or in some of the others in the next few years. A disease model in pigs would provide unprecedented opportunities for identifying the Alzheimer’s process and testing new drugs,” says Arne Lund Jørgensen.

At the same time, he stresses it is not certain that the pigs will develop Alzheimer’s.

“But the project could be valuable nonetheless because even a partial disease model, in which pigs develop certain aspects of the disease, may be useful in the testing of pharmaceuticals.”

In parallel with the Alzheimer’s project, other Danish researchers have created pigs with genes that can cause atherosclerosis, just as “psoriasis pigs” are on the way.

Blood Self Test Saves Lives

In Vejle, Denmark, patients take blood tests themselves – at home. It saves lives every year, writes Nadia Louise Kristensen in Focus Denmark Nr. 3 2010.

At Vejle Hospital patients are taught to take blood tests themselves – another area where the hospital is helping to think in new ways.

A little finger prick, then up comes a number on the screen.

Blood cells. Photo by www.sxc.hu.

It shows how quickly my blood clots. Had I been a real patient taking the test at home, I would only have had to turn on my pc, open a little programme and enter the number. The figure would tell my doctor if I needed more or less anticoagulant medication. From a remote location, the doctor can see my reading – I can even write a comment to the doctor if I have any concerns. The programme can also calculate the most appropriate dose and a lot else besides, which is a good thing when comparing and analysing patient data.

The programme, called CSO/AC, has been developed in collaboration with the Danish company IntraMed and is used by increasing numbers of Danish hospitals. It can be used both for patients receiving anticoagulant medication and for patients with diabetes. In Denmark, the little programme saves lives.

“Every year, 500 people die in Denmark because of insufficient anticoagulant medication. Without this system, patients only receive proper medication 60 percent of the time. With CSO/AC, the figure is 80 percent. None of those patients who are testing themselves have been hospitalised with blood clots,” says Ivan Brandslund, who is laboratory manager at Vejle Hospital.

Besides saving lives, it also means that a physician can attend to many more patients. Using this system, Ivan Brandslund can look at the numbers and adjust the doses of 20-30 patients in one hour. If he had to see the patient each time at the hospital, he would only be able to attend to six patients in an hour.

The part of CSO/AC which calculates doses is in use in several clinics in the US, where it makes a big difference. One of them is the Medical Center of Plano, Texas: “Our clinic has about 900 active patients. All patients enrolled into our clinic are added to CSO. The dosing suggestions of CSO are considered, but of course the nurses make the clinical judgment regarding dosage changes. The system has aided our ability to track 900 patients in a very organized and efficient way, despite our volume,” says Kim Williams, a nurse at The Medical Center of Plano, Texas.

Denmark is a relatively small country where the nearest hospital is never far away. But in countries like USA, Canada and Australia, where there can be great distances between people and hospitals, CSO/AC has even greater promise, opines Martin Couët, Channel Sales Director at IntraMed, which is a distributor of CSO in the US: “This product has got a lot of potential. The healthcare providers can manage more patients with the same resources. The patients can save time and money on transportation while being more in control of their condition. And in countries like USA and Canada, as soon as you get outside the big cities, it can be a challenge to find qualified nurses and physicians.”

The Health Care System’s Smart Robots

Outside the film world, robots are hardly as colorful and charming. They can do amazing things – but it is not always easy to see, writes Nadia Louise Kristensen in Focus Denmark Nr. 3 2010.

A window of a Denmark home in Kolding. Photo by www.sxc.hu.

At a hospital in Kolding – a small town in Denmark – there is on one of the many long corridors, a black box containing something reminiscent of the bullet chamber of a revolver. On each side of the box is a pipe not much thicker than a garden hose. The parts constitute the Tempus 600 robot, a small revolution in the world of blood test collection. The revolving chamber is not designed to contain bullets, but blood sample tubes, which are shot down the pipe with a hissing sound at 7 metres per second, or 25 kilometres per hour. In just 43 seconds the tubes arrive in a metal tray at the haematology lab. Tempus 600 is still being tested to see if the blood samples are damaged by the high speed transit, but so far it appears that they are damaged more by being transported on a hospital trolley than by Tempus 600. When the robot is fully integrated, it will not be a person who retrieves the blood sample from the metal tray – everything will be automated so that the samples are automatically centrifuged and analysed, and the test results relayed to the digital screen of the relevant physician.

Robots reduce waiting time

The revolutionary aspect is that the machine can reduce the time interval between a blood sample being taken and the doctor receiving the results from 3-5 hours to 30 minutes.

“Staff are expensive to run. When they transport something, it uses up time. They have coffee breaks or just chat to a colleague on the way. Robots are cheap to run and very reliable. If a person takes a blood sample and then delivers it, it can take a long time. The person must first collect a batch of 10 blood samples before delivering them. It can easily take an hour, and then at least ten minutes to deliver the blood samples to the laboratory,” says consultant Ivan Brandslund, who helped conceive the idea of the robot together with the Danish company FagTek Vacuum System A/S.

“A blood sample waiting on a table is a patient waiting in a bed. It costs money keeping a patient in a bed. The staff patient ratio is about 5:1, so you save money if you save patient waiting time. It is a question of reducing waiting time throughout the system. And there are limits to how much we can push people,” says Ivan Brandslund.

FagTek Vacuum System A/S, which has developed the system, is noting great interest both in Denmark and from abroad.

“The interest is quite overwhelming. We have not yet started sales activity, but we have already been contacted by several major companies such as Abbott in Sweden, Norway and Switzerland, and Siemens in Denmark and the US. They are all interested to know if the Tempus 600 is really that easy to operate. The other pneumatic transport systems on the market are complicated to operate. With Tempus 600 you just take the blood sample tube and put it in the hole, then you can go off and forget all about it,” says Daniel Blak, director of FagTek Vacuum System A/S.

Robots reduce waiting time

The revolutionary aspect is that the machine can reduce the time interval between a blood sample being taken and the doctor receiving the results from 3-5 hours to 30 minutes.

“Staff are expensive to run. When they transport something, it uses up time. They have coffee breaks or just chat to a colleague on the way. Robots are cheap to run and very reliable. If a person takes a blood sample and then delivers it, it can take a long time. The person must first collect a batch of 10 blood samples before delivering them. It can easily take an hour, and then at least ten minutes to deliver the blood samples to the laboratory,” says consultant Ivan Brandslund, who helped conceive the idea of the robot together with the Danish company FagTek Vacuum System A/S.

“A blood sample waiting on a table is a patient waiting in a bed. It costs money keeping a patient in a bed. The staff patient ratio is about 5:1, so you save money if you save patient waiting time. It is a question of reducing waiting time throughout the system. And there are limits to how much we can push people,” says Ivan Brandslund.

FagTek Vacuum System A/S, which has developed the system, is noting great interest both in Denmark and from abroad.

“The interest is quite overwhelming. We have not yet started sales activity, but we have already been contacted by several major companies such as Abbott in Sweden, Norway and Switzerland, and Siemens in Denmark and the US. They are all interested to know if the Tempus 600 is really that easy to operate. The other pneumatic transport systems on the market are complicated to operate. With Tempus 600 you just take the blood sample tube and put it in the hole, then you can go off and forget all about it,” says Daniel Blak, director of FagTek Vacuum System A/S.

Designed for efficiency

At neighbouring Vejle Hospital, where Ivan Brandslund works as a consultant and laboratory manager, one can see how the hospital of the future can be formed both in terms of technology and the way in which the various wards are equipped. Previously, laboratories were scattered around the various hospital wards. Over time, these laboratories began using many of the same technologies to handle their work – technologies which are still very expensive. By bringing together all the laboratories in the same building, staff can share the use of equipment, which both reduces equipment costs and minimises the time spent going from one place to another.

It became the start of a new building, which several Danish experts in streamlining working procedures have declared to be so efficient that they cannot see anything that needs to improved.

“Part of what makes the building unique is that, right from the start, we put strong emphasis on flexibility, so that the interior layout can be adjusted. User requirements change over time, and so it is essential that the building can do likewise,” says Niels Bøge of Søren Jensen Consulting Engineers, which helped plan the laboratory building.

Vejle Hospital’s laboratory building has served as a model for other hospitals, including Bergen in Norway, Santiago in Chile and Lund in Sweden.

The square building is five stories high, with the technical facilities housed in the centre.

“Having the technical facilities in the centre means that the distance to the places they serve is very short. This makes it easy to move installations when needs change,” says Niels Bøge.

It is not only cheaper and more efficient to run the laboratory in this way. It also results in more research and collaboration.

“When heads of laboratories talk to each other, so do their specialist staff. There is competition between these specialities – but also a synergistic effect. The academic level, quality and research all went up after we moved together. To put this in quantifiable terms, the number of articles we publish in international medical journals each year has risen from five or six to about 50,” says Ivan Brandslund.

Robots are the future

A few years from now, patients admitted to Vejle Hospital will be the first in Denmark to have a blood sample taken by a robot called Roblood, developed in collaboration between the University of Southern Denmark, Vejle Hospital, the Danish Design School and others.

“There is great potential in robots. We can streamline a lot of processes and enhance quality. The robots will perform the simple activities, so that staff can use their time and resources to care for seriously ill patients. The net effect will be to provide a better service with the number of staff that are available. A comparison can be made with craftsmen: if they have a power screwdriver, they can increase their work rate and produce better work. With robots, we can improve our offering and provide services to more people if our healthcare and nursing services adopt the technology in the same way as craftsmen and ourselves,” says Anders S. Sørensen, an associate professor at the University of Southern Denmark.

At present, 11-12 million blood samples are taken annually in Denmark, and each year the total increases by about seven percent. More diseases can be diagnosed by blood samples, and most treatments require that regular blood samples are taken. The pressure on staff is thus continuously increasing.

“Our goal is to develop a technology that can take the pressure off the haematology labs. The staff in outpatient clinics have more and more tasks to perform in the same period of time. They make the same movements day in, day out, which result in injuries to wrists and elbows,” says Professor Sørensen, who is involved in the competence network RoboCluster, where educational institutions and private sector businesses are working together to create a new generation of robots.

The technical challenge is to create a robot with three-dimensional awareness. It must both be able to locate a vein, know where the needle is, and keep the patient from moving about or be able to change course if the position of the vein moves a little. This is what the University of Southern Denmark and Vejle Hospital have just started to test.

Professor Sørensen reckons that Roblood will be fully functional in 5-7 years.

Both at Vejle Hospital and the University of Southern Denmark, they believe that the future will bring variations of Roblood.

“Robot technology is becoming increasingly sophisticated. Over time, robots might be used for other things – for example inserting an intravenous drip. What is almost impossible is to get robots to perform functions where they need to take complex decisions. If there is a cup on a table, how should it be picked up without spilling it? It’s easy if all cups are identical. The more well-defined the work the robot performs, the easier it is. Robots designed to show care, for example, are very difficult to develop because showing care involves a lot of information and many decisions,” says Professor Sørensen.