Scientists in Estonia forge weapon to beat Ebola

Photo: Margus Ansu

Estonia is not untouched by history’s largest Ebola virus epidemic outbreak in Western Africa last year. Not in the frightening sense, though. Rather the opposite: in a week or two, we might preach some glad tidings.

A two storey grey and fully renovated Soviet time building at the edge of Tartu... an unlikely spot for three-four folks to be testing and trying about means to beat the extremely deadly Ebola. What’s more, to top all that the building features kindergartens. The kids are not to camouflage the scientific research of global significance, a life and death issue for tens of thousands in near future.

The kindergartens are just tenants in a building into which, at the beginning of last year, academician Mart Ustav moved his bio tech firm Icosagen – till the end of last decade known as Quattromed.

It was at the end of last October that Icosagen came face to face with the infamous Ebola virus, up to now claiming the lives of close to half of those infected i.e. about 10,000 people, but which in the worst case scenario may kill nine of ten. And, mind you, the kindergarten kids sharing the same building poses no threat so: parents have peace.

Fighting at own expense

By last fall, it was evident that Ebola would not be over anytime soon. For many a scientist around the world, this was a push to begin searching for vaccine and medicine against the virus which for close to four decades keeps raising its head and then subsiding.

One was Icosagen’s technology director Andres Männik (42) who, about a dozen years ago, defended his Doctoral thesis on papillomavirus under supervision of the very Mr Ustav.

Mr Ustav recalls they naturally had a debate in the company whether it was worth the effort, seeing the virus would hardly touch Estonia. «But very well,» he thinks back to the positive decision. «Let’s keep it far from here, then.»

With a staff of half hundred, Icosagen namely has the technical means and experience to throw against Ebola. The firm has developed, produced and sold biotechnological products the world over, from Malaysia to USA, says Mr Ustav stretching his arms wide. The turnover reaches over €2.5m a year. «Every year, we make a small profit,» adds Mr Ustav. «A couple of hundred thousand.»

Now, the profitability comes in handy. Because, to fight Ebola, the firm undertook at its own expenses – not by some research grant acquired from someplace.

This is risking, venturing, admits Mr Männik – only time will tell if good will come, to Icosagen and the humankind.

Time to get busy

Though the initial known Ebola outbreak happened in 1976 – at a small tributary to Congo River named Ebola, in a village called Yambuku, where 280 died of the 318 infected – till today neither vaccine nor medicine has been found for it. Some, indeed, are in the stage of clinical tests.

Can’t be ruled out that a reason for the not-so-enthusiastic reaction by scientists and pharmaceutical companies has been due to the disease contained to Central Africa mostly. So what if, as early as end of last century, the bestselling American author Tom Clancy came out with a warning novel «Executive Orders» wherein terrorists from Middle-East attack USA with the very Ebola.

Last year, however, Ebola reached outside of Africa. In the fall, and American got it – and died eight days later. At the end of the year, the initial Ebola case hit England.

By the time Ebola made it into Europe, Mr Männik had already begun his antivirus research. Once upon a time, interest towards biology had been sparked in him by the famed science teacher at Tallinn Lilleküla Gymnasium, Linda Metsaorg. While at his Doctoral thesis in University of Tartu molecular and cell biology institute, he also begun working at the Tartu research and development department of the Finnish biotech firm FIT Biotech, toiling at development of HIV vaccine and immunological medicines. When FIT Biotech closed down its Tartu department four years ago, Mr Männik joined Icosagen.

The decisive push into the fight against Ebola was both Mr Männik and Icosagen having formerly dealt with viruses and antibodies. Antibodies are organism defence molecules which ought to recognise a virus and start fighting it. Thus, for starters, all they had to do was engage knowhow obtained in former work.

The way the Ebola virus operates is simple, actually: it enters various cells in the organism and makes these reject their tasks in the organism. Instead, the cells start to produce new viruses and soon disturbances develop with blood coagulation, usually ending with organs like liver, kidneys and lungs failing. Death comes a week or two after the symptoms have occurred, mainly high fever (38.9 °C and above) with pain in joints and muscles, nausea, diarrhoea and vomiting.

Cheating to win

To fight the cell-enslaving Ebola, Mr Männik says there are two solutions. First, infection must be hindered i.e. the entry of virus into cells prevented. This means vaccination. Secondly, if the virus still managed to enter some cells, the infected cells with the virus in them need to be destroyed while hindering new healthy cells from being infected. That means treatment.

Vaccination means that, among the tens of millions of antibodies i.e. defence molecules in an organism, one needs to find such as will recognise Ebola virus and begin to fight it, forming these into antivirus memory, explains Mr Männik. In his words, potential treatment will be people injected antibodies produced outside his body, in a so-called cell factory, which will tie themselves to the virus so it can no longer enter cells. Thus, a viral disease is overcome.

But with this, there is a trick which at the first glance seems dangerous – and might make the kindergartens next to Icosagen anxious. (But will not and must not, let it be immediately added.) Namely, in order to find antibodies fighting against Ebola, theoretically one would need the very Ebola virus itself. Because, how else will one find the suitable defence molecules – these would have to be called forth with the virus itself.

Even so, in the light corridors and white laboratories of Icosagen, one will not meet scientists and staff in air tight space suits as in any Hollywood movie on the virus. With only one lab, while entering one must take off his shoes – no other precautions.

The trick, allowing battle against a deadly virus next to kindergartens, is the Icosagen staff using fake goods to find the right antibodies. They are not using Ebola virus, but particles resembling it. These pose no threat, as the virus itself is absent. Which means the little children may attend kindergarten in peace and serenity.

To explain the trick in some depth, we may use something like ... bears.

Imagine a brown bear: hairy on the surface, a predator inside. Now, compare it to a teddy bear: also hairy, yet totally harmless. Touching them with a finger in the dark, one may not tell the difference. 

Mr Männik is convinced that an organism will also make no difference if an intruder is a murderous virus or a peaceable virus-like particle. Such particles are prepared by scientists, growing human or animal cells in containers – the so-called cell factories.

To get a virus-like particle, all one needs to have is two proteins of Ebola virus. As cell factories are set to produce these virus proteins, virus-like particles bud out of cells. Such particles can be collected as harmless and non-infectious analogues of Ebola virus.

When virus-like particles are injected into organism, the organism will recognise these as alien bodies and will begin to produce antibodies to counter them – a so-called memory is created. As the virus-like particle resembles the real Ebola virus, the body will next time as attached by the real Ebola virus quickly recognise it and render it harmless.

Tests abroad

Yes, in theory this sounds simple and logical. As explained by Mr Männik, the problem lies in how, while manipulating the virus proteins, to achieve such antibodies as will be most effective against Ebola – the kind that will indeed hinder Ebola virus from entering cells, not limited to recognising them.

For that, animal testing is needed. As an example of that, scientists inject virus-like particles into a rabbit and. In a couple of months, inspect the animal’s blood serum to see how many antibodies have been created – and how good is their quality. When satisfied with the results, the scientists can get the genetic information of the antibody of their interest from the spleen, blood or bone marrow of the animal – where the cells that produce antibodies are located. After that, such antibodies can be produced in the cell factory, researching if these could be used to make a life saving medicine for Ebola-infected people who have not managed to be vaccinated. 

The success of these tests in Icosagen’s labs will be found out in a couple of weeks as the initial results come in. As confirmed by Mr Männik, at least the production of virus-like particles has been rather successful. Also, he is sure they will definitely find the antibodies that recognise the Ebola virus. But will these antibodies prove capable enough to be used in treatment of Ebola, this is also a matter of luck, he adds.

Should Icosagen issue good news bringing hope for production of Ebola vaccine and medicine, for the next half year the Estonian scientists will have to hand things over to colleagues in Switzerland or France. Icosagen simply lacks the technical means to finish the development of vaccine or medicine. What’s more: that’ll take a higher level biological safety lab – in Estonia, to build and to maintain such will be beyond anybody’s means.

As Icosagen finishes its part, immunologic virology lab staff at Lausanne University or the French atomic energy agency will find out if the virus-like particles are effective as vaccine when macaques and guinea pigs are infected with real Ebola virus – will animals actually infected be cured by the antibodies?

With loose ends abounding, Mr Männik would rather not predict when an Ebola virus vaccine or medicine might be ready, and how much it would cost. This is not up to him or Icosagen at all. Meanwhile, he is not setting hopes up too high, saying that towards the end of the work it may all fall to pieces – if an effective vaccine or the healing antibodies aren’t fount after all. 

But he does not take a tragic approach. Firstly, the work towards Ebola vaccine or medicine has not been too much of a burden for the company: three-four of the staff have done it at the side. Secondly, the antibodies found during the research will be part of the company’s intellectual property, allowing these to be patented and marketed.

«For us, this is a development project of very low risk,» notes Mr Männik.

But, should it succeed, it will be worth a whole lot for the whole world.

THE MERCILESS VIRUS

Till last year, the major Ebola outbreaks only hit a couple of hundred people; this one, however, has already touched over 23,000, close to 10,000 of whom have died.

Year	Ebola sub-type	Cases	Deaths
1976 (Zaire)	Zaire	318	280
1976 (Sudan)	Sudan	284	151
1995 (Zaire)	Zaire	315	250
2000–2001 (Uganda)	Sudan	425	224