“LIVE SCIENCE AT BIOTALENTUM LTD, GODOLLO, HUNGARY”

Antonia Dalla Volta

When young journalists meet great scientists to explore the secrets of one of the most discussed
contemporary field: the so called “Stem Cells”. Can we really use them for curing treatments? Is it
really ethical, or not? The organised practical courses seem to have positively impressed all our
journalists.

The first day at BIOTALENTUM LTD, Godollo, Hungary, has immediately been a full-immersion
into the main issues, apart from a fully appreciated interruption the staff did to warmly welcome all
the journalists taking part to the workshop, offering tea, coffee and delicious traditional puddings.
After that, it was Prof. Andreas Dinnyes who gave us a brief introduction to the entire workshop,
entitled “Training on Stem Cells and Nuclear Transfer Cloning Technologies”, explaining the
importance of genetic research, as well as scientific knowledge in general, for the health and benefit
of the human kind.
Given that all of us were scientific journalists, he insisted on the main features every aspiring
scientific communicator should have, like being professional, able to tell juicy stories, to maximize
the media’s attention, to keep the information corrected and non-distorted, aware of the risk coming
from tabloid and commercial tv stories…
It was an exemplar lesson on scientific writing.

CLONING AND STEM CELLS

“Stem Cells” are known as the precursor of all the different kinds of cells an individual has; the
earlier we go back in our development, the more able our stem cells appear to be at producing new
cells.
If stem cells are pluripotent and undifferentiated, on the contrary the new cells created starting from
the stem cells will differentiate into different cell types (such as skin, muscle, bone, etc.).
“Dolly” was the first mammal to be cloned, in 1996, by nuclear transfer from adult cells. A risk
assessment run in 2006 judged animal cloning perfectly safe. The species cloned till now are horses,
cats, rats, rabbits, sheep, goats, pigs.
Although cloning might be good for therapeutic reasons (“human therapeutic cloning”), there are
some fields where nuclear transfer cannot be tolerated,e.g. the “human reproductive cloning”, or
bringing back Tasmanian tigers, and so on…
Therefore cloning has got some limits, regarding its outcome.

PRODUCTION OF TRANSGENIC CELLS AND ANIMAL MODELS

The first thing we had to pay attention to was this statement: ”There is a lot of false perception,
nowadays, of transgenic technology”.
The main reason for developing transgenic technology is connected with medical purposes, such as
creating genetic resistances to diseases, or using animal’s organs for transplantation into humans
(“Xenotransplantation”), or genetically modified animals as disease’s models, to study diseases
such as Alzheimer, cancer, and so on. The mouse, for instance, can be used as an animal model in
genetics in different ways: a) forward genetics-phenotypes; b) reverse genetics-transgenic
technology, which enables scientists to “create” the kind of mouse they need, with the feature they
need.
Nowadays, many of the above mentioned medical purposes can only be afforded in medical labs,
but in ten years from now it might be possible for example to routinely transplant animals’ organs
in human beings.
Scientists use ESC (Embryonic Stem Cells), which are pluripotent and can be derived for instance
from the mouse embryo, to introduce genetic alterations to mammalian cells.
Mario Capecchi, Martin Evans won the 2007 Nobel Prize for Physiology using the “Gene Targeting
Strategies”, which enabled them to differentiate the ESC into muscles, or nerves, or every other
tissues in at maximum two weeks, and then to introduce them into humans. This kind of knowledge
is at the basis of the so called cell-based therapies on human beings.

INDUCED PLURIPOTENT STEM CELLS AS NEW TOOLS FOR FUTURE GENERATIONS

Pluripotent stem cells have the capacity to become any cell in the body. There are different types of
pluripotent stem cells: a) embryonic stem cells; b) induced pluripotent stem cells.
Whereas in pluripotent stem cells a specific set of genes is active, that is required for maintaining
their pluripotentiality, the majority of somatic cells have that set of genes inactive.
Induced pluripotential stem cells are very similar to Embryonic stem cells: there are many ways of
differentiation for the pluripotential (stem) cells: a) in vitro; b) in vivo (throughout an injection).
These cells can be used for research’s purposes, conservation’s purposes (endangered species),
pharmaceutical studies, therapy.
Looking at the “cell therapy”, today it is applicable to the gene therapy too (e.g. “hemoglobine gene
mutation”).

FLUORESCENCE MICROSCOPE
Scientists need an appropriate equipment to study and see the stem cells, such as a good
microscope. The different kinds of microscopes can nowadays be divided into:
a) OPTICAL MICROSCOPE;
b) ELECTRONIC MICROSCOPE;
c) ATOMIC FORCE MICROSCOPE (which enables people to see not only the cells, but the cell’s
nucleus too);
d) MONOCULAR MICROSCOPE ( it is an inverted microscope).
There are also useful tools we can use, able to transmit our movements, and fine enough to work
with cells. One of these is the “Micromanipulator”, which is connected to the microscope
(pneumatic micromanipulator), so that I can do very fine movements, such as embryo-
manipulations.
Others are, e.g., the “microcapillar”, the “microforge”, or the “microgrinder”.
The main use of these sophisticated microscopes is related to the possibility of analysing, e.g., the
embryos for every inherited diseases (pre-implantation diagnosis), or to see whether the embryo is a
female or a male.
Scientists are able to manipulate the embryos throughout a “bisetting”, which is able to divide the
embryo into two different parts, which will give birth to animals absolutely identical. That’s
cloning.
As already told, cloning is possible from a)embryonic cells, or b) somatic cells.
Given that genetists need engineers for appropriate tools to perform their work, the scientific
industry is a very good business nowadays.

MICROINJECTION AND CHIMERA TECHNOLOGIES

Thanks to the genetic modification of the stem cells, we can introduce or remove some genes, and
study the functions of the genes.
E.g., scientists made a female mouse think she was pregnant through an induced superovulation.
After that (which requested an operation), these animals woke up pregnant, although it was not
really so!!!
However, the mouse thinks of being pregnant, and it starts preparing its uterus for having a baby.
After the superovulation, scientists use a fertilization process, which leads to the development of an
embryo. Fertilization can happen either “in vivo”, or “in vitro”.

PRACTICAL COURSES

A) CELL SPLITTING
We have been trained how to use pipers with two stops: the first to put in the liquid, the second one
to take out the liquid. We will need it to isolate the stem cells.
Seen at the microscope, there are aggregations of stem cells, up to one hundred cells for every
aggregation. These cells are alive, and floating.
We examine a tissue culture, looking how do stem cells look like, if they are healthy or not.
Our trainer firstly showed us how to do the experiment, during which we see how do the cells look
like a) before the experiment; b) after the experiment.
Before starting the tissue culture, everything must be sterilised with gamma-radiations; then, the
cells will be differentiated. It usually takes ten days, but to do it faster you should use the abscorbic
acid. This is the splitting of the cells. We could see stem cells differentiated in hearth’s cells, which
had started beating.

B)EMBRYO COLLECTION
Given that the goal is to get gamets from the mouse we need to kill mice, to get sperm cells.
The proceedings involve: a) removing cumul cells; b) sperm collection; c) in vitro fertilization.
Scientists will kill a male mouse to collect the sperm from it; before doing it they have to use
hormones to induce into them a superovulation, because they want to minimize the number of mice
being sacrificed. They will buy a part of the animals (specifically bred for experimental reason, or
they purposely breed them).
Usually they work in sterile environment, with pipets and scissors. When working in the lab, they
usually wear caps and masks to protect their faces.
Firstly, we collect the embryos, using then a solution to keep the pH stable; we collect some drops
of these liquids. After we prepare and enzymatic solution which will help us to get only the oocytes
inside the cell.
We are working on oviduct, ovary, uterus. We move the oocytes from different drops, in order to
analyse them. Then, we looked at the sperm with the microscope. Once isolated the sperm, we
united it to the oocytes, and the day after we have an embryo.

C)MOLECULAR BIOLOGY
We have seen movies about DNA, Dna replication, transcription of DNA to RNA, translation of
RNA to proteins, and also about how to the HIV virus works into the cells, spreading itself to the
other cells. It is a multi-stage process: a) how the virus attaches the human cells; b)its shape,
resembling the human genoma, is able to cheat the human cells. Scientists think that in ten years
from now it will be possible to replace diseased cells with stem cells. That’s why science is so
important, because patients, thanks to it, can be cured and lives longer lifes!!! Moreover, progresses
are increasing very fast in these fields, the technologies to reach this goal are already known…
Then, scientists showed us how to cut out and to isolate the DNA from the cell; they were also able
to determine the concentration of the isolated DNA in the sample they had taken.

I am just a journalist, not a scientist, but taking part to this MY SCIENCE PROGRAMME really
helped me to realise how important science is to cure diseases, and save human lives.
I will not be able to cure patients, but dealing with scientific issues I hope I might contribute to raise
more and more awareness of the scientific research.
Chimeras - what you and a mouse can have in common

Aleksandra Budzyńska

Dismissing myths about scientific research. What are pluripotent stem cells and how thanks to mice
we will able cure genetic- based illnesses in the near future.
Myths, said an ancient Greek Salustios, are “things that never happened but always are”.
One of numerous myths tells a story of chimera. It was a monster with head of a lion, body of a goat
and tail of a snake. Nowadays there also are chimeras. Maybe even you are one of them: “if you
have older brother or sister, you're chimera” says Dr. Andras Dinnyes from Biotalentum
laboratories, Hungary. In scientific terms chimera is an organism that has two or more genetically
different cells which come from different zygotes. It may occur naturally; sometimes just cells of a
fetus may remain in a mother body, even for years, and then “join” to those of a new fetus. A
“chimera”- person can have, therefore, two different DNAs depending on the part of the body! It is
very uncommon to detect, however, as a series of DNA tests should be done.
What about animal chimeras? They are not scary at all. Usually they are laboratory mice, mixes of
black and white ones. First mice chimera was created in 1981 by a Pole - Andrzej Tarkowski.
Sometimes to their genes some color markers- green or red are added in order to follow more
specifically the phenomena which are investigated. Scientists (and we too as in fact scientists are
working for us!) need those animals in order to better understand some processes going on a micro
level. This is because embryo division of mice, human, bovine and the other animals are very
similar on the first stages. In addition to that breeding of mice is the best suitable for sterile
conditions which must be kept in laboratories.

Mice chimeras Fot. Biotalentum

Currently the top research is those upon induced Pluripotent Stem (iPS) cells. Pluripotent means
that a cell may undergo further “specialization”. It has a potential to become a somatic cell -for
example a skin cell. First time they were derived in 2006 from mouse and just one year later from
human. In pluripotent stem cell a set of genes are active, which are required for maintaining
pluripotency whereas in somatic cells most of these genes are inactive. They may be differentiated
in vitro and in vivo alike. IPS cells are very similar to embryonic stem cells in their characteristics.
This is very important because the latter have capability to self-renew themselves. Therefore, they
may be very helpful to cure serious diseases. It may be done in two ways: by
cell replacement therapy for e.g. cardiac diseases, diabetes, Parkinson disease or by gene therapy.
e.g. sickle cell anemia. First in principle seems to be easy: somatic cells are taken from a patient
then de-differentiated in order to derive from them somatic cells and then differentiated again into
healthy, somatic cells again. In order to do so, chimeras are needed to follow and evaluate the whole
process. Scientists from Biotalentum are studying among others signaling pathways involved in
pluripotency and this is only one of their many tasks.
In English language the term chimera has also come to mean hard to believe or difficult to
understand. But now, you know that it is not a case! Just to end with another ancient sentence:
sapere aude (dare to know)!
Can skin become a liver?

Tobiasz Lemański

At the beginning of your life you consisted of a few almighty cells, which could create every cell of
your body. With a new iPSCs technology, every cell of your body can become almighty again. This
means, that obtaining a liver or heart from your skin is possible.

When you were a small child, you would have had a chance to become anybody you wanted: pilot,
doctor, or prime minister. Getting older slowly deprived you such a great variety of choices. If you
spent majority of time playing football you have a chance to be a professional sportsman, but you
cannot convert to, for example, pianist. With time passing, every person becomes more specialized.
The same thing happens with our cells. At the beginning of the life, human being (called then
embryo) consists of very few cells. They can be transformed into every cell of the organism and be
part of either muscle or brain. This magic feature, which I named ‘almighty’, is known among
scientist as a ‘pluripotency’.

Pluripotency is specific for stem cells. The ones, which exist at the beginning of organism’s
development are called embryonic stem cells. However, in many adult tissues, including bone
marrow, muscle, and brain, there are cells, which have similar feature. These adult stem cells can be
changed into other types of cells. Our body uses them to replace those, which were broken during
injuries or diseases. In contrast to embryonic stem, adult stem cells cannot become all cell types of
the body – their abilities to differentiating is limited. But they have one important advantage over
ESC. Tissues produced by adult stem cells are believed less likely transform into cancer cells and if
they are derived from the same patient, they will not initiate rejection after transplanting them back.
This feature is very important from medical point of view.

The process of cells specialization is studied in deepth for at least two reasons. First of all, it can
makes us better understand cancer and birth defects, which are caused by problems occurring
during this process. Another potential application of pluripotent stem cells is producing tissues for
medical therapies. Many people have damaged organs and they desire new heart, kidney or liver.
However, the number of people needing a transplant is much higher than the number of organs
available for transplantation. Using stem cell lines it may become possible to generate, for example,
heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart
disease. Thanks to this technology not only heart diseases could be healed. In the future, many other
disabilities, including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns,
heart disease, diabetes and arthritis, would be treated.

Possibility of obtaining a renewable source of replacement cells and tissues is too tempting to not be
used. Many scientists want to work on it, and the best material for research are artificially fertilized
embryos. During in vitro fertilization there are often embryos produced, which are not going to be
used for reproduction purposes. - There are tens of thousands frozen surplus embryos, in every
developed country because of the human in vitro fertilization program. They are waiting in liquid
nitrogen to be thrown away. – explains Andras Dinnyes, professor of the Szent Istvan University,
Gödöllő, Hungary, and director of BioTalentum Ltd. But there appears a question we should answer
before allowing scientist to work on it: is an embryo a human being? If so, that would mean killing
ones for healing others. If not, researches would not have the ethical dilemma.

The questions has no simple answer. There are many arguments for and against granting embryos
human being’s rights and not only the public, but also legislators are divided. On one side, an early
stage embryo does not look like a person, does not possess nervous system to feel pain or to be
conscious and cannot become a newborn individual without implantation into a women’s womb. On
the other hand, it is programmed to be a born child in a few months, possesses all genetical
information needed and its process of becoming child proceeds continuously. As a development is a
continous process, there are different opinions where there is a start point of „life as an individual”.
Everybody agree that there is no life before fertilisation. But when exactly? Different people give
different answers.

Respecting the diversity of opinion in ethic matters we do not need to abandon dreams about
plantation of hearts or livers. There is a new, equivalent technology, which overcome dilemma of
destroyed embryos. Adult cells, can be genetically reprogrammed to an embryonic stem cell-like
state by genetically engineering so-called pluripotency factors into them. It means, that skin cells, or
any other cells, which are already specialized, can become pluripotent again and change in every
part of the body. These nduced pluripotent stem cells (iPSCs) seems to bring very similar results as
embryonic stem cell lines. - So far analyses show, that they amazingly versatile and capable to
differentiate to other cell types. However, this technology is very young and we still have to see if
they are really, truly and clearly equivalent to embronyic stem. – says professor Dinnyes.

iPSCs are already useful tools for drug development and modeling of diseases, but scientists hope to
use them in transplantation medicine. However, years of research have to be done before that,
because not all is clear about the safety and side effects. Currently the most serious problem
concerns introducing factors, which reprogram the genom to become pluripotent. So far viruses are
used, but this process is not fully reliable: in some studies viruses used in this technique caused
cancer. Researchers are investigating non-viral methods, which can be more safe and enable iPSCs
be more applicable.

Probably it is not much time waiting for results. Science goes on so fast.
The day we journalists put on our white aprons

Lorea Arakistain

For a week fifteen journalists from all over Europe have put on white aprons, gone into the lab and
become scientists. The reason, biotechnology, and the scenario, the BioTalentum laboratory in the
Hungarian town of
Gödöllö. There they work with stem cells, they clone animals… a scenario that can lead to
controversy, that’s why it is attractive for us journalists.

And so is the country. Hungary joined the European Union in 2004; and in 2005 the Hungarian
Government established its science strategy; the Hungarian Government is in fact keen to be the
European leader in the field of biotechnology so it can compete with Asia and the United States.
There’s nothing new about its link, because the term biotechnology was first used by a Hungarian,
an engineer called Karoly Ereki, back in 1919. And people at the BioTalentum laboratory, one of
the 70 companies that exist in the field of biotechnology in Hungary, continue the work he started.

With little more to go on, 15 of us from the UK, the Netherlands, Italy, Bulgaria, Lithuania, the
Czech Republic, Poland and as many other countries arrived at 09.00 hours one morning ready to
put up with temperatures of 10 degrees below zero. We had been selected by the EURAC
organisation to take part in the My Science programme. With a single aim: to train professionals
and provide them with resources so that they can be the go-betweens in the work to increase the
understanding of science among European citizens. The chosen ones share two characteristics: they
are journalists and they are young.

We were welcomed by the scientist Andras Dinnyes. He set up the BioTalentum company, and the
moment he opened his mouth I understood why we were in that laboratory. That is where Klonilla
the mouse was born, the first animal to be cloned in Hungary. It was followed by Tapsilla the
rabbit. That’s no coincidence. Dinnyes worked at the institute where Dolly was cloned, and when
he felt the conditions were right he returned to his home country.

Before we donned our white aprons we discussed ethics, ways of doing journalism, and science
communication. We were totally in tune: knowledge has to be shared. Difficulties will come up.
Scientists always prefer the news to be upbeat; but journalists not necessarily. And the journalist’s
limitation is often the deadline, having 24 hours to contrast the results of 20 years of research that
he or she has received by means of a press release. That is what happens and that is how it will
happen.

Then came the presentation of the researchers. Some are easy to look up in the Encyclopaedia of
Science and Technology; and among them there is the occasional one that needs a bit more. They
also come up with phrases that could be turned into titles: “We are bound to be eating cloned
animals,” or “we’re working with techniques that our society does not find totally acceptable”. But
Asia and the United States are doing it too, and that’s where the competition is. What are we
supposed to do? Forget about everything and then import from those places?

After that the procedures. Unfortunately, instead of getting to see the animals live, we meet them on
a video recorded previously in the lab upstairs. And there’s nothing I would like more than to see
where the animals live. Snooping too much? Perhaps. On the screen we see an operation being done
on a mouse before it is tried out on a human being. Anaesthesia, scalpel… Thinking it could be used
on Teknopolis I ask for the video. You’re free to ask… and the person asked is free not to grant
your request. “This is not a show,” replied Dr. Ana Claudia Carstea. She’s afraid, afraid of the
animal rights activists. She doesn’t reckon the general public is ready to see the work done with
animals. If that’s the case, that is what we journalists have to do.

Two days, masses of information, reams of notes and after as many cups of coffee we are ready to
go into the lab. Having put on white aprons and gloves, we get involved in the absolutely basic
work. We look through the microscope. “Look, sperm cells rushing around”. They could have been
anything… but sex always works in headlines. Pipettes, centrifuges, the importance of sterilization,
cutting DNA… we’re doing mechanical work. Big things are done in laboratories with instruments
that look small but which cost a bomb.
We play. And everything we touch ends up in the bin. Just in case! We’ve spent a week in the lab;
but outside with a glass of beer in our hands –why not?– we take time to speak at length and in
depth. The Hungarian scientists have shown us their knowledge and their work. They have told us
everything without any complexes as long as the camera isn’t there. But Dr. Szilard Bodo is
prepared to talk on camera; but about his private life, not his work. He doesn’t seem to have
permission for that. If you want to be the leader, you will have to move to the front of the race.

The race is on. Showing the enemy, in this case the competitor, all one’s strength has never been a
good strategy for winning. Right. But how are we supposed to tell people about the race that we
have not seen directly and which cannot be shown live? We can talk about what we’ve been told,
we have been able to put on our white aprons, but we have told people about the race once it was
over. They didn’t even know that the race was going to take place.

And many other races are also run. Naturally, we want to be the first at the newspaper offices, too.
Living with researchers who work with difficult, complicated subjects has been a good experience.
Would it be a good experience for scientists to take off their aprons and spend a week in the
editorial office? The gauntlet has been thrown down. Anyone is free to pick it up.
How will be the life with pig livers?

Veronika Piterova

Pig is very similar to human, speaking from the physiological perspective. Its organs such as heart,
livers or kidney work quite similarly to ours. Therefore, in future pigs could replace the human
organ donors.
Gödöllő (Hungary) – It might seem like science fiction, but so called xenotransplantation or using
animal organs for human patients, is likely to be a suitable solution for this field. Of course, it could
be possible only under certain conditions and after overcoming number of obstacles. However, pigs
are so far the hottest candidates to become new rescue workers.
Widely known and used pattern human-human could be replaced by new pattern: human- pig.
Human’s heart which underwent the heart attack might be changed by beating of piglet’s heart,
similarly livers destroyed by alcohol could be switched for the pig’s one. And patients, who have to
go through the dialysis to clean their blood, could be given the pig’s kidneys.

Extra clean pig

Not all pigs are convenient for this purpose. Therefore, individual pigs targeted to be the organ
donors would have to live a very sterile life full of tests to avoid the eventual transmission of
viruses and bacteria diseases. To minimize the risk, they would have to be bred in absolute
quarantine. Scientists also evoke the possibility of creation genetically modified pig for this
purpose.
“If we manage to create such a pig, it will become universal donor which will facilitate everything,”
says professor András Dinnyés (BioTalentum, Gödöllő, Hungary).
Even human donor must be tested for eventual bacterial or viral contamination. Furthermore, the
virus might be hidden even inside the organs and couldn’t be visible for the first sight.
“In this case, genetically modified pig would be safer donor, because we could avoid the disease’s
transmission from human to human,” adds professor Dinnyés.
The research on xenotransplantation is also supported by European Commission. Scientific teams
from several European countries, such as Italy, Great Britain, Netherlands and Switzerland, are
involved.
„This project is running. Technology is there, now we just need to finish it,” says professor
Dinnyés.

You will not grunt

The most likely candidate to be transplanted first seems to be a kidney or a liver. Concerning the
pig’s heart, complications may emerge due to the fact that people walk on two feet compare to pig’s
walk on four feet. Therefore, the human’s organs undergo bigger pressure and pig’s heart valves
might not cope with that perfectly.
But there are other questions to be answered - for example the duration of pig organs’ operating
life. Will the organs have to be replaced after several years? Scientists don’t know yet. Similarly, it
is not resolved what will happen if a ten-year old receives piglet’s heart. How much will the organ
grow within the human body? This issue is particularly crucial because otherwise it would be like
having the latest model of the computer with the software from ten years ago.
Also financial or economical potential needs to be taken into consideration.
“Genetically modified pig will be costly. Same as when we have cloned the first piglet, it was also
very expensive. But the second one was cheaper, the third one even cheaper and today it is
reasonably priced method,” says professor Dinnyés.
Whether it will be with pig’s kidney or liver, patient should not feel it is an animal organ.

Pig’s life
Pig seems to be the most applicable donor also for other reasons. Killing pigs is generally accepted
because no pig - no Wiener schnitzel.
However, some obstacles may emerge, particularly due to the religious reasons. For example
Muslims and Jews consider pig as unclean animal.
„ Maybe we could transplant monkey’s organs as well. But here we meet the problem of how
monkeys are accepted within the society. Moreover many species are protected, they are also more
complicated to be bred and all over, the genetic engineering if this field is far behind that the
research about pigs,” explains professor Dinnyés.
Another complication could be human mentality. In relation to pig, majority of us still imagine
piggery, stench and grunting.
“If somebody will be dying and will have two possibilities – either to die or to try it out with pig’s
organ, I believe, that many people would choose the second option,” adds professor Dinnyés.

You can’t stupefy human body

However, the biggest obstacle of xenotransplantation is the immune system. Human body is very
sensitive and the warning red light usually appears even after transplanting of human organ which
has at least the same contexture.
You can imagine what happens if you force the body to accept a tissue from different species, i.e.
from animal. It is like when you refuel the petrol to the Diesel engine.
Unlike the engine which you can’t persuade to any activity, scientists have the means to stupefy
human immunity and avoid its hysterical reaction. But similarly to sickness pills which can
aggravate the attention and you are advised not to drive a car, the faint immune system does not
protect the body totally and viruses and bacteria are free to do to their job.

What else?
The lack of suitable organs for transplantations is very current issue, because people are dying all
over the world. Xenotransplantation is one of the possible solutions. Scientists don’t want to guess
when the first pig organ might be transplanted, however they would like to realize it within a
decade. On the other hand is it also possible that by this time completely new technology will be
discovered and xenotransplantation will be left aside.
Professor András Dinnyés has been dealing with embryology, cloning and stem cells since almost
25 years. Under his direction, the first cloned piglet was created; similarly the first rabbit and mouse
in Hungary. In 2005 he created institute BioTalentum specialized in agriculture, medical and
pharmaceutical technologies. Prof. Dinnyés is lecturing at Szent István University in Gödöllő.
I believe our discoveries can make a difference in the life of many

Djoke Hendriks

Dr. András Dinnyés is worldwide known for his expertise in research into reproduction and
biotechnology. He tells us why and how the communication between science and society has to
improve.
Can science do anything it wants?
“Personally I think we should focus on research with a potential positive impact on people. We
should strive to improve the quality of life. That is why I moved away from the agricultural science,
where I started, to the biomedical sciences. It has a stronger impact on people’s lives. After all,
science is influenced by the “market” and there is a push for applied research. As scientists, we
need feedback from the society for what can be applied and what cannot at a given stage. Scientists
often do not consider the big picture; they always think they are doing something interesting. But
there are limitations in investing public money in things that nobody wants, whether that is for
ethical or economical reasons. As we are using public money, market research before investing that
money is well justified and fair. But on the other hand, not every research can and has to be directly
applicable, as we need discoveries from basic sciences to improve the scientific world and pave the
way for a better future. After all, in science you should expect the unexpected; otherwise it’s not a
scientific discovery at all.”

Is cloning extinct species and pets a waste of time and money?

“Certain issues would have an immediate positive impact, creating novel medical model animals in
rabbit or rat – projects I am working on, or for example endangered species preservation. But
although cloning a mammoth may sound exciting to a ten year old, it’s really a commercial
business. Imagine it, every zoo would order one. A panda costs 1 million dollars to rent as the
animal and all its progeny remain Chinese property. Imagine what a real life mammoth would cost!
That would mean big business and great publicity for cloning but it would not change or improve
society. I personally believe that it’s better to invest money in biobanking: to store the tissues and
somatic components of existing species and individuals for the future, when it might be technically
possible to clone them.”
How do you feel about the way society deals with your area of research?
“Sometimes I feel happy and sometimes sad. Most people know about the research and some are
excited about it. But it’s the details they don’t understand. The image is distorted through the media,
politicians and interest groups. Most people do not understand the potential benefits before I would
talk to them about the details. But there is no time to discuss these with every person on the planet.
So that’s why media sources are crucial. But it is hard for lay people to know which article is
reliable and which is not, since pro and against articles appear every day. I think that journalists
need much more scientific training as they would need to have a clue about what they are writing.
It’s the same with sports or art: You should not comment on a football game when you do not know
the rules. I think it is naive to say that someone with no knowledge about science will write a better
and more objective article.”
Why is the communication between science and society so hard?
“Science is often handled as an ivory tower because to do it you need lots of knowledge and you
specialize more and more – including the proper terms and vocabulary. That’s why the
communication is so difficult as scientists often are not able to explain what they do in simple
terms. Unfortunately, usually there is no science communication training at the universities.
Scientists should try harder and they should be trained in this. Of course not every scientist will be
good at it; there are more and less talented communicators. Universities should do much more, as
EU- research programs typically have communication courses for scientists and students.”
Is the research climate in the EU good for science?
“It varies depending on the topic and the country. In the EU animal research and the use of Human
Embryonic Stem Cells are strictly regulated. In Hungary I’m a member in the regulatory advisory
bodies helping the government and the Academy of Sciences to formulate a better policy. This way
I’m paving the way for future scientists, as well. Novel scientific discoveries, such as for example
induced pluripotent stem cells, are coming out so fast that the regulations cannot cope easily with
the novel scenarios created by them. I have a strong interest in that stem cell type in humans and
become the first to obtain a permission to use them for research. Only with a company setting up, I
was able to react on the new discoveries so fast – Universities are much slower.”
Do you feel that the rules are too strict?
“Rules are very important as they provide a frame for the work. But political influence on sciences
is another issue. When in the Netherlands they had cloned the first bull named Herman, it was very
advanced-stage work worldwide. But then the government decided that it was too risky and the
company had to move the animal to Finland and later to the US for freedom to do that line of
research. When politicians think something is risky they just intervene even if the regulations and
rules are not there and often they do not understand the techniques. When President Bush in the US
did forbid the investment of public money into human embryonic stem cell research, the only thing
that happened was that the transparent public institutions were forced to stop their federally funded
research. But the private companies could carry on and nobody would know what they were doing
exactly. That’s obviously not the best way of dealing with such issues.”
How should we then deal with these controversial issues?
“Communication between scientists and key stakeholders, including patient organizations, industry
and politicians should be started in a very early stage. This would allow a better legislation to be in
place by the time a new discovery starts to be applicable. Of course, this is a bottom up approach
compared to the typical paternalistic top-down regulatory systems.”
Do you understand the skeptical views from society?
“Society has the right to be careful and conservative. Being skeptical is a bit more sad, as it reflects
the fact that scientist failed to balance the negative side effects with the positive benefits of the new
discoveries. Furthermore, scientists often made exaggerated promises, under pressure from media or
grant agencies. And there is a payback time for every mistake. However, if we look at the progress
we can expect, as a scientist, I am not skeptical at all – I strongly believe that what we might
achieve will make a difference in the life of many.”

Additional info on András Dinnyés:

(Dinnyés was team leader for the team that generated earlier the first cloned mammalian
worldwide, a sheep named Dolly. Later, he also cloned the first animal in Hungary, which was a
mouse with the name Klonilla. Currently, he is a professor at Szent Istvan University in Gödöllö,
Hungary. Furthermore, he is the founder and CEO of BioTalentum Ltd, a research company which
works on transgenic animal technologies and stem cell technologies, especially on embryonic and
induced pluripotent stem cells. His company has numerous international cooperation’s and plays a
leading role in several European Union financed research projects.)
The Hungarian Xerox

Ieva Nora Fīrere

Even though cloning has slipped out of the hottest issues of science, the technologies are still being
improved for the sake of animal well-being, says the team of Hungarian scientists who earned their
fame by cloning a mouse and a rabbit several years ago

The first three hours in Hungary come along with a bunch of disappointments – crappy public
transport, grim people and service in the best socialist traditions. However, finally we get to see the
reason why we have come and will stay here for a week. Cold January night covers the Hungarian
Institute of Biotechnologies in darkness, leaving the roof shining. It’s made of glass and the lamps
are left on, illuminating the life of laboratory animals. The building also hosts the facilities of a
world renowned scientific research company BioTalentum Ltd. Since the European Union is ready
to pay for scientists and journalists improving their communication, BioTalentum has agreed to
welcome young reporters from various countries.

Lobbying science
Before the world media caught the news regarding the birth of the first cloned creature in Hungary,
there was a slight mistake. The mouse was born some weeks earlier than Klonilla, but then was
eaten by the mother. This wouldn’t make nice publicity, therefore the team held a pause until the
beginning of November, 2006 when they could announce the birth of Klonilla. The first ever cloned
mouse in Hungary was a result of three years hard work in the field of nuclear transfer technologies.
Media eagerly published the story selling it together with the next ambitious project of the institute
– to clone a rabbit within two years. Cloning a human would be irresponsible since the cloning
process is still imperfect, at that point said professor András Dinnyés. He is the head of
BioTalentum and is praised for his lobbying skills, which attracts money to the company. Professor
Dinnyés is also well aware of the advantages of publicity, therefore kindly became a host to 17
journalists.

The Dolly school

When it comes to geneticists, professor Dinnyés is well known in Hungary and abroad. The man
just celebrated his 44th birthday by Victoria Falls and in the name of science has been moving
around quite a bit. He studied and worked in New Zealand, Japan, China, USA and UK, where he
was attached to the Scottish Roslin Institute, famous for cloning sheep Dolly. The national media
cites him and the professionals pay their respect, although it hasn’t always been like that. Ten years
ago the local science stars troubled his ambitions. «When I came back, I was too young for the
position I was really eligible for because of all the publications and all my track record. So there
was a big conflict,» he says with a touch of bitterness. He was about to leave but then decided to
give home country another chance by founding a company that combines science and business.
BioTalentum Ltd. was formed without venture capital, says Dinnyés. «We don’t match the typical
goals of very high return rate and quick exit strategies. I’m doing lots of research that will produce
results in five or ten years. If you don’t get potential exit within three to five years, you are not a
good investment target,» he says and smiles: «I did my MBA, I know».
A gigantic blood rabbit
One of the shelves in his cabinet resembles an altar. White fluffy creature takes almost all the space
there, leaving a tiny plastic mouse besides it look even smaller. It’s the honor he pays to the first
ever Hungarian clones – mouse Klonilla and rabbit Tapsilla. When results of the study had been
collected and Tapsilla reached a considerable age, the cloning team decided for euthanasia.
Professor gets slightly irritated every time when looks at the white rabbit. Not because of cloning
technologies, rather because of the bad job done by taxidermists. «Tapsilla was so cute, little, round
and cuddly, but they made it this wide, like a blood rabbit,» he says and keeps forbidding any
photography.

Out of fashion for a while

The aim of cloning is not to produce large amounts of identical animals. «Especially not with mice,
because they are very closely genetically related animals, sisters and brothers are mating, etc. So
cloning basically is a tool of developmental biology. We can analyze the genes and investigate
various functions of genes. Another purpose is to produce a genetically modified animal, for
example when a human gene is inserted in a rabbit, some other gene is replaced or knocked out,»
says dr. Szilard Bodo. He is a colleague of prof. Dinnyés and one of the 20 people who were on the
genetic reprogramming team. Technologies are left incomplete and there is still room for
improvement. There should be fewer abortions, retardation and cancer cases and, even thought the
great focus has shifted away from cloning, science is still working on it, they both say.

A peripheral breakthrough
During the huge cloning race in the ex-socialist countries Hungarians were competing with the
Polish scientists. «I was going for the a mouse, they were working on a rabbit. It’s not crystal clear
if they actually did it – I never saw a publication,» remembers Dinnyés. Now, when the race is over,
other hot topics like stem cells have aroused. More challenges and more grant money there, says the
professor. Currently his team is working on cell replacement theory, cardiac and nervous tissues.
BioTalentum has managed gathering specialists from so many different countries, Rumania, China
and Thailand included. A couple of Hungarian specialists have moved back from the US. Hungarian
brain drain has been taking place since the 1940s. First because of political reasons, then because of
economical, says the professor and reminds of the atomic bomb, which was partially invented by
the Hungarian – Jewish scientists, who managed to escape to the US. Science in Hungary has
always been and still is very developed. During the Soviet times it was due to the location –
Hungary was in the periphery of the Union and managed to keep closer contacts with the West.
«We managed to get some information, materials and technologies passed on. The Russian
scientists used to benefit from that». Now Dinnyés is consulting scientists in countries that were
once united by the USSR.

Europe invents, the US uses

When it comes to the consumption of cloned meet, Europe has stayed pretty conservative. On
contrary the US, South America and Asia are open to the chances this technology provides. The
professor says it’s due to the overproduction of food that Europe still has, and it simply hasn’t
occurred to the Europeans that cloned food has the advantage of being cheaper. «Europe prefers to
listen to the bio food producers, who say – what we grow, is much more expensive, but at the same
time safer and better». At the same time when Europe can say that it’s clean of cloned animal
products, there is still opportunities of cloned animal sperm getting here. «It is very funny, because
this kind of cloning was developed in Europe, so the innovation originated here, but is used and will
be used in the next couple of years primarily in the US, South America and Asia. It’s not the first
time when innovation is done here but other benefit much more».

Extreme opposition
When cloning is on the agenda, dr.Bodo starts at 8 AM and finishes at 2 AM. They work with live
beings so time maters and scientists have to adapt. «It’s hard to combine private life and job of this
sort. The family doesn’t tolerate it,» says Szilard and then adds – on contrary to the family, the rest
of the society is getting more and more understanding about his profession. Once a week Szilard
teaches at school and pupils there have stopped calling him a killer, he smiles. It’s quite the
opposite in the UK, where scientists have had challenging times lately. Pressure of the extreme
animal rights defenders keeps growing. When Dinnyés was working there, neither his address nor
any other contacts appeared on the institute website. Otherwise it would endanger his wife and
daughter, aged 6 now. «If you fear scientists, is very contra productive, because scientists are
actually there to resolve the issues you are facing. So it is a sign of immaturity, if the society fears
scientists. Fortunately it’s not like that in Hungary,» says Dinnyés. Later in the train to Budapest,
Andreas from the journalists’ group would reveal that he has completed a course in how to work
with animals in a lab. It turned out that the first issue on such a course is how to identify and how to
handle various kinds of bombs. He is merely pretending to be a journalist and actually doing his
PhD in cell biology and had to learn the bomb lesson to start working with the animals.
Cloning is a tool, not the goal

Eva Vlčková

In 2006 prof. András Dinnyés used somatic cells to clone "Klonilla", the first of such mice in
Hungary, and generated Tapsilla, the first cloned rabbit in Central Europe, one year later. In 2000-
2001 he was team leader for the group which previously cloned Dolly, the sheep at the Scottish
Roslin Institute. He is founder and director of a Hungarian biotech company Biotalentum Ltd based
in Gödöllö, 30 km from Budapest. In January his company hosted an EU funded workshop for
young European journalists called “My Science Programme”.
A few years ago you made headlines by cloning the first mouse and the first rabbit in Hungary, a
first for all post-communist countries. But what is the sense of repeating the same results that other
teams had achieved before you did?
What is the sense of building a nuclear reactor in the Czech Republic when they built them in the
United States much earlier? We want to use the technology therefore first we have to set up a lot of
technological elements and perfect them to the level that it would work. Cloning of animals is not
the goal, it is just an enabling technology which can be used in biomedical research. It is a key
technology to create genetically modified (GM) animals including potential model animals for
Alzheimer disease or cardiac pathologies and many others.

When you worked in Roslin Institute your team created the first genetic knock-out lamb.
What are such animals good for?
Knocking-out genes improves the technology of creating genetically modified animals. GM mice
have been here for a long time. If you use very fine genetic engineering it gives you much more
accurate results with less side effects. To achieve this goal first you need cell cultures. In those you
can create the rare modifications you want only contained in one in ten thousand cells or one in
hundred thousand cells. You select these cells and create the animal from them.
In mouse this has become the basic technology thanks to the existence of mouse embryonic stem
cells and has been awarded by a Nobel prize in 2007. In other species, lacking embryonic stem cell
lines, this can be done only by cloning: using somatic cells, doing the modification, selecting the
cell that you really want and then trying to create the animal from it.
A lot of people get scared when you say "GM animal". Do they have any good reason or are
they just scared of the new technology in general?
I think that the latter is closer to reality. New technologies sometimes are very powerful and people
are concerned with them because we experienced lots of misuses - starting from the dynamite to
atomic energy. But it is not the scientists nor the technology to blame. It is the people and how they
use the technology which can result in misuses, too..
Most GM mammals like GM cows pose very little danger. GM viruses or bacteria which have been
around and used for many decades would be potentially much more dangerous because you can
easily detect and monitor a cow - but not a bacteria. But we are using GM bacteria all around
Europe for example to produce enzymes used in cheese making and nobody complains.
Maybe people don´t know it...
Probably they do not care because it is "only" bacteria. People care much more about GM cow or
pig but actually traditional breeding is also genetic modification, just by a slow process of selection.
In traditional breeding you always choose the best properties and keep them for next generations.
But cloning is only copying. So what is the sense of using cloning in agriculture then?
You can copy the superior animal, multiply its genetics and distribute it in a horizontal way very
quickly. Not from one generation to another but broaden it in one generation. This can be
economically beneficial. Of course the important point is not to loose genetic diversity in the same
time. But it is another issue and there are techniques to preserve it.
But it means you have to suppose that you have the best possible animal.
Yes, at that moment. Like a top-bull whose sperm is very much wanted all around the world. But it
is changing every other year - and that is the economical value of cloning. Only in very high
individual value animals and with very broad distribution of their genetic material we would have
the added value sufficient to justify the expensive procedure. That is why cloning is used only in
cattle, horses and sometimes in pigs. Breeding of sheep or goat is not so intensive so it would be
probably not worth to clone them for agriculture. But it might be worth to clone and genetically
modify them for biomedical research.
Why do you think it is possible to use cloning in agriculture in the USA but it is perceived
problematically in Europe?
Society is different in the US and in Europe. Also the profit in cattle business is different and most
of the top genetics come from the US. They are ahead of Europe in this area. So if they are using
new technologies, they can increase their advantage because they have what to distribute. Also their
approach is different - there is an economic reason and benefit - the American public appreciates
that. In Europe the interest of agriculture producers is perceived differently by the general public
and animal welfare issues are much more emphasized.
But on the other hand American approach to human embryonic stem cells research is more
complicated than in Europe.
I don´t think so. If it would have been that way, many of the states would not vote for opening up to
this line of research. It was problematic for the central, federal government, but it was Republican
party opinion which did not fully reflect the general opinion. Even in Europe it is partially about
politics. Also, the public perception is shaped by different media and interest groups.
What is your personal opinion on human cloning?
First you have to distinguish between therapeutic and reproductive cloning. Therapeutic cloning –
to produce cloned human embryos only then using them for embryonic stem cell generation for
biomedical research - is acceptable and allowed in several countries. However, even this technology
might have new alternatives with the fast advancement of stem cell methods.However, reproductive
cloning is not safe at all using the current technologies. It would results in many sick babies, dying
during pregnancy and even after birth. This technology at the moment is not ready to be used in
humans, although scientists still improving the methods in different animal species. Anyway, it
would be probably extremely difficult to get any authorization for trying reproductive cloning on
humans as it is strictly forbidden all around the world. And I doubt how useful this technology
would be - there are other techniques of human reproduction available and adoption of kids is also a
very important, socially positive alternative.
Scientists and the general public

Andreas Alber

Some thoughts from a scientist about the importance of science communication

Nowadays public engagement seems to become increasingly important as new technologies and
products arise from newest scientific research. Especially, genetically modified products and animal
testing are discussed controversially in the general public. Recently, I had the opportunity to participate
in a workshop about science communication from the MY SCIENCE programme of the European
Union which inspired me as a PhD student doing basic research to write this short essay.
In my opinion public engagement and media work will become more and more important. Lots of new
technologies were developed in life sciences during last years which will lead to a variety of new
products. But is the general public ready for transgenic food, gene therapy and ethical issues that come
along with it? I think people might be if they are well informed. It is the responsibility of the media to
inform the general public. But not only, also scientists and research centres have, in my opinion, the
responsibility to inform the general public as well as collaborate closely with the media. A significant
part of research is funded by public money. Thus, scientists should not hide themselves into labs.
From a discussion with Prof. András Dinnyés, co-founder and director of Biotalentum Ltd. where the
workshop took place, emerged that especially proactive communication from science would be
important. For example, it is the case that organisations like Greenpeace and animal rights organisations
are campaigning very actively against gene modification and animal testing. However, both can result in
huge benefits for humans. Genetically modified food may have the potential to improve the famine
situation in big parts of the world; gene therapy could cure so far terminal illnesses and animal testing in
research and drug development is simply necessary if we do not want to test directly on humans. The
question is if science wants to stand up more actively against inaccurate campaigns or not. I think more
could be done to inform the general public. In that way people may become less susceptible to
scientifically inaccurate information.
Animal testing is always a hot and ethically controversial topic and a good example for insufficient
communication in my opinion. Animal rights organisations are very actively campaigning against
animal testing. However, there is no way around animal testing at least in science as it is an important
step in basic research as well as drug development and safety testing. To date, no alternative method is
available. It is also questionable if real alternatives in scientific research may become available in the
future as the aim of animal work is often to test for the unexpected in a whole organism. How should a
computer programmes or artificial cell cultures be able to reach this goal?
The use of animals for experiments is strictly regulated by law. I think this is very important to avoid
unnecessary experiments and minimize animal suffering. But, even if strict regulations are in place and
animal testing is important the opinion of members of the general public is often more negative than
positive. Is that really because of the animal work itself or due to a lack of information? I think the lack
of information plays an important role. Scientists often do not speak or are not allowed to speak about
animal work. The main reason for it is safety. Sadly, it is the case that radical animal right organisations
pose a threat to institutions and individual researchers. But is it really the right way to minimize or even
stop communication therefore? In my opinion that may lead in an even a more negative climate in the
general public if science does not try to explain why they are doing animal testing. Thus, active
campaigning is mainly done by organisations that purposely select only very controversial examples
with no aim to explain why animal testing might be important.
Concluding, I think that the importance of science communication is increasingly recognized in Europe.
It seems to me that more an more institutions and mass media channels are trying to actively bring
science to the general public or are already doing so.
A 60 line intro
What remained in my head after My-science workshop in Hungary

Vera Gotseva

This text could have had many different beginnings. It would have passed through its inevitable
middle where I would share my own biased views on science in general. There I would express my
concerns over scientists turning into the new heroes of cool, of science turning into cheap,
newspaper mainstream. I would have reminded the readers how often, because of its financial
dependency, science serves to “politically correct” (for one corporation or other) decisions. I would
also have reminded everyone how un-famous those scientists are, who dedicate their whole lives to
the search of answers to questions we all ask. At the end, I would have admitted that despite all of
this, I trust in scientists, because they are human, too.
To back up my statements, I would have chosen one of the many interesting topics which were
brought up during my visit at the Biotalentum institute. During the one week I spent there, I felt like
Alice, whom the scientists took by the hand and walked through a whole new world, proving how
real and possible things we think are absurd actually are. How you can create life after death (by
uniting an egg and a sperm by already dead lab mice). A scientific world in which I saw how
stunningly beautiful it is to extract DNA fragments. A world of cells connecting to other cells
connecting to other cells, ad infinitum.
But out of all this diverse and interesting information, what struck me the hardest was something
mentioned randomly during one presentation. A scientific fact which put everything else aside.
Imagine a playground full of kids. Some of them are hanging off the jungle gym, others are huddled
around the sandbox. Paul and John* are pushing the swing where their three year-old daughter is
sitting, along with all other mothers and fathers. This fantastic future is not a continuation of Aldous
Huxley’s Brave New World, but a real, tangible chance to have their very own children that many
gay couples like Paul and John actually have. It sounds absurd and incredible, but it is actually true.
At the end of January, I and a group of other journalists from various European countries had the
great chance to meet one of the most prominent scientific figures in genetics – professor Andras
Dinnyes who founded the Biotalentum institute in Hungary. This man is an icon in the world of
genetics, and those who have not heard his name are very few. The fact that he was part of the team
of scientists who worked before on cloning Dolly the sheep in the 90s is the least that can be
mentioned about him. A much more interesting fact is that Andras Dinnyes is an inspiration to
many, as much with his scientific findings as with his positions on a myriad of ethical questions
linked to them.
It was Professor Dinnyes who mentioned during his presentation that: Male ESCs can be turned into
eggs as well as sperm. Two men could both be biological parents of a child, with a help of a
surrogate mother. It’s very important for a gay marriage, but the society is totally unprepared for it.
And with his words, he brought up not one, but two important issues. Of course, it is easiest to
suppose that these issues concern the stability of our moral system and playing God – issues which
accompany any possible deviation from what is perceived as natural and normal; issues which are
the shadow of everything connected to genetics today and which are often used as a comfortable
battlefield by moralists, politicians, scientists, doctors, journalists, democrats, liberals,
conservationists, and others. But if we dig deeper, we’ll find that everything boils down to two
much clearer issues.
The first one is that society constantly has to catch up with scientific progress. It’s enough to take a
look back at all the scientific achievements from the 20th century in order to see how true this is.
The second issue reminds us that even scientists are part of today’s society and sometimes they
have to catch up with their own selves. And here comes the most interesting bit.
The scientific fact shared by Professor Dinnyes became subject of a wholly human evaluation only
two days later, where in an off the record conversation, one of the scientists confessed that it is
perhaps best for gay couples to use the much better known to us in-vitro method in order to
conceive children. This means that sperm from one of the partners can be connected to an egg and
carried by a woman. It also means that only one of the partners can be a biological father. Scientist
explained this with society’s unpreparedness and his belief that some things must remain natural.
What he mentioned was part of a longer conversation and went by quickly, but it could not not
leave an impression on everyone, and this was not only due to the fact that the scientist was actually
taking sides in a quite painful debate. Actually, taking it this way would have been a hasted
reaction, because neither this scientist, nor the rest of the scientists at Biotalentum actually stand by
conservative beliefs. It’s just that what the scientist said actually threw the ball back at society and
reminded us all how unprepared we all are for the idea of two fathers both being the biological
parents to one child. And it brings up the most important of all questions – how flexible is the
border between what we want from science and what we can accept from it? I have my answer. I
leave yours up to you.
Because this text could have been written in many different ways, but it would always have had the
same ending – In science I trust.