By: Kourosh Ziabari,
Valadkhan, the world-renowned biomedical scientist and the
Assistant Professor of Case Western Reserve University of USA. She
is the 2005 winner of AAAS Young Scientist Award.
Dr. Saba Valadkhan is a world-renowned biomedical
scientist and the Assistant Professor of Case Western Reserve University of USA.
After graduating from the Tehran University of
Medial Sciences, Saba Valadkhan moved to New York where she could continue her
further studies at the Columbia University upon the fellowship which she had
been granted from RNA Research Society.
This young Iranian scientist has won several
international awards for her effective, determinant contribution to the field of
Molecular Biology such as Peter Sajovic Memorial Award, Harold M. Weintraub
Graduate Student Award and James Howard McGregor Prize.
In 2005, she was awarded the American Academy for
the Advancement of Sciences (AAAS) award of Young Scientist of the Year for her
breakthrough in understanding the mechanism of spliceosomes which was something
unprecedented and innovative until that time.
By developing a new strategy to prevent the
occurrence of some disastrous cancer types, she identified and determined a
slight and insignificant deficiency in the functionality of DNA strands and
found an effective way of solving it.
Following is the text of exclusive interview with
Dr. Saba Valadkhan in which a stack of interesting subjects around the details
of her latest discovery, scientific community of Iran and the prospect of
research in Iran and has been discussed.
Dr. Valadkhan; we know that your landmark
discovery in understanding the actual function of Spliceosome lead you toward
receiving the prominent 2005 AAAS Young Scientist Award which was a honor for
all of Iranians, rather than yourself. Would you please elucidate for us that,
in a simple and general language, what your discovery specifically was and how
much it would be useful to solve RNA-related problems practically?
Human genome has many fascinating features, but
perhaps one of the most interesting is the fact that our genes come in
fragments. In our genome, we have between 25,000 to 100,000 genes, depending on
whom you ask. Now each human gene is on average divided into 8 fragments, but
some genes are divided into as many as 100 fragments.
As we all know, our genetic information is stored
in DNA strands, which are very long, thin linear polymers, just like very long
strings of pearls, except that instead of pearls we have DNA nucleotides
adenosine, guanosine, cytidine and thymidine. You can think of them as four
different types of pearls, of four different colors, for example. Our genetic
information is stored as the sequence of these four DNA nucleotides, for
example, two adenosines followed by three guanosines mean: the product of this
gene should be taken to the surface of the cell, and so on.
Now imagine that the gene that has the
information for making hemoglobin is divided into three fragments, to use a
simple example. It means that after a certain combination of nucleotides that
indicate the beginning of a gene, we have about 300 nucleotides that constitute
fragment 1 of hemoglobin, followed by 5000 nucleotides that are not part of the
hemoglobin gene. Then we have another 250 nucleotides that form the fragment 2
of hemoglobin, followed by 3000 intervening nucleotides, and finally, 180 bases
that make up the last fragment of the hemoglobin gene, followed by a certain
sequence of nucleotides that indicate the end of the gene. Clearly, in order for
our bodies to make hemoglobin, these fragments should be put together.
The way that this is done in our bodies is that
whenever our bodies need to make hemoglobin, they make a copy of the hemoglobin
gene from the start sequence to the end sequence, this contains the three
hemoglobin gene fragments and the two long stretches of nucleotides that
separate them. Then, the beginning and ends of these intervening sequences are
recognized by the cell, and they are removed, and the three hemoglobin gene
fragments are attached together. Only then, after all the extra sequences are
gone, will this copy of the hemoglobin gene be used by the cell for making
This process, the removal of the intervening
sequences that separate gene fragments, is called splicing, and the group of
molecules in the cell that perform this job are collectively referred to as "the
Now imagine what would happen if splicing is
performed incorrectly, for example, if the beginning of the second fragment of
hemoglobin is mistakenly recognized as part of the intervening sequence. Then,
the spliced copy that is used by the cell will lack the information that was
contained in the beginning of the second fragment, which can result in a
hemoglobin that cannot bind oxygen. Red blood cells are made, but they cannot
function. Or conversely, if part of the intervening sequence is by mistake
recognized as a piece of the hemoglobin gene fragments. Then, we have extra
information that might tell the cells, by mistake, that the resulting hemoglobin
protein should be rapidly destroyed by the cell.
The result would be a severe lack of hemoglobin,
although the cell is making a lot of it. The clinical outcome of both cases
would be Thalassemia. And these were just two of the many possible problems.
Remember that each human gene, on average, has 7 of these intervening sequences,
and that every time our bodies need to access the information in our genes, they
need to make a copy of the gene and splice it correctly.
At any given moment in the cell, there are more
than 200,000 copies of different genes that are used for various cellular
functions. Now you can see how incredibly critical splicing is. One mistake is
enough for one cell to die or become severely ill. Indeed, it is thought that
more than half of all human genetic diseases are caused by mistakes in splicing.
And splicing-related diseases are not limited to genetic diseases. Any disease
with a genetic element, such as cancers, neurodegenerative diseases such as
Alzheimer's, etc, can result from splicing mistakes.
I hope I have convinced you by now that splicing
is a very important cellular process! The spliceosome, which is the assembly of
molecules that perform splicing, is extremely complicated, as expected. However,
this complexity prevents us from understanding its function. Thus, despite all
the human tragedies caused by splicing-related diseases, we are very far from
understanding the problem and curing it. What I did was to make a simple model
for the spliceosome, which allows us to understand this critical process.
Clearly, this opens the door to understanding how splicing-related diseases
happen and hopefully, finding a cure.
With all of your explications, we see
that a great respect is being paid to the "Molecular Biology" that is your
academic major of study, but seems to be somewhat less known in Iran and the
rest of Middle East, as well. What kind of biology branch is it and which sort
of subjects it deals with?
Molecular biology is in fact an approach to
biology, rather than a field of study. In molecular biology, we try to
understand biology at the level of molecules: which molecules are involved in
each biological process, how they interact with each other, and how they are
made and destroyed by the cell, when necessary. You can use this approach in any
field in biology, from neurobiology to botany to microbiology, molecules govern
how living cells function, and molecular biology can tell us exactly how these
It is an extremely powerful way of approaching
biological questions, and these days it is impossible to have an in-depth
knowledge of biological phenomena without employing molecular biology. A very
large share of new discoveries in medical sciences is based on molecular
approaches. For example, in modern cancer therapy, screening of the population
for early detection, diagnosis, classification and treatment are all based on
molecular biology approaches. Molecular biology has already revolutionized
medicine and will continue to do so in the future.
It's more than 15 years that you are far
from your homeland, Iran. Do you have still some scientific relations with
universities and institutions inside the country? Are you enthusiastic to return
to Iran someday if the preliminaries of a substantive scientific environment for
you are provided satisfactorily?
I am trying to forge scientific relationships
with the Iranian research community, and I am hoping to have a broader
interaction with the Iranian scientific community in the future. I am
unfortunately not very familiar with the status of research in Iran, but I know
that the number and quality of scientific publications from Iran have been on
the rise, which is a very encouraging sign Hopefully this trend will continue.
The status of science seems to be improving in
Iran, however, the infrastructure is still a concern, and interaction with the
broader scientific community is still very limited. These factors prevent the
science enterprise in Iran to achieve its full potential. Hopefully with
effective planning, sufficient funding, and the cooperation of the scientific
community these issues will become less of a hurdle in the future. There are
many talented scientists currently in Iran that if given the opportunity will do
great things. I want to stress that we don't lack talent or skill, what is
limiting science in Iran is the lack infrastructure and the right type of
environment. Even if all the Iranian scientists currently living abroad return
to Iran, there will not be any significant changes in the quantity or quality of
scientific productivity in Iran until these shortcomings are addressed. Now if
the government solves these shortcomings, the scientists currently residing in
Iran are more than qualified to do cutting edge research.
2005 file photo (by Saman Aghvami, ISNA)
So is it going to be fair that we conclude Iran lacks the basic fundamentals and
accouterments of effective scientific, research works to be carried out in?
See, I have young Iranian scientists in my
laboratory that have previously performed research in Iranian universities. They
all agree that in terms of equipment, they had all they needed in Iran, that is
they had better equipment in Iran than they do in my lab. They also had easy
access to research animals and human tissues or samples, for which we need to
conduct three months' worth of paperwork in US. What seemed to be limiting their
research was access to reagents, many of which were ordered from abroad and took
a long time to arrive and perhaps more importantly, not appreciating all they
had. We Iranians have a tendency to see the empty half of the glass, and this is
something that hopefully will be alleviated by more extensive interaction with
laboratories abroad. There are shortcomings everywhere, so we all need to use
our talents and energy to overcome them.
Therefore, what causes that a load of
young Iranian talents leave the country each year to abroad and make us
encounter the phenomenon of "Brains Escape"?
I think this is the wrong way of looking at the
problem and in fact, it's not seeing the real problem at all. In Iran, we can't
complain about brain drain, we have many more educated, trained forces than can
be gainfully employed. We don't need any additional educated work force; we
already have more than the country needs. The real problem in Iran is that the
country spends a lot of resources training medical doctors or physics PhDs and
they can't find jobs that match their training and end up doing carpet business.
Our problem is brain inflation, not brain drain. It is not that educated people
choose to live and work abroad despite having equally good opportunities in
their home countries, the issue is that they don't have acceptable choices at
home. Nobody enjoys the often very painful process of emigration, but lack of
opportunities forces many to leave their home countries. And let's not forget
that after these "overflow" educated forces leave, they often remain committed
to contributing to their motherland in any way possible. There are many
prominent Iranian academics abroad that have made significant contributions to
the human society that have made all Iranians proud, and that continue to
contribute to their homeland by transferring their knowledge through teaching in
universities and workshops in Iran.
If we put the work force aside, we can
take a glance at Iran's scientific stride from the view of scientific indicators
including ISI, as well. What are the most remarkable ones among these indicators
and what they narrate about Iran's research productivity?
There are many such indices and depending on whom
you talk with, they might prefer one or the other. I think a reliable way of
measuring the level of scientific productivity in the biomedical field is the
number of publications in Pubmed-listed journals. Number of publications in top
tier journals in biomedical fields, Science, Nature, Cell and the New England
Journal of Medicine, is a good indicator of the quality of scientific work done
in a country. I took a moment and calculated these numbers for Iran and a number
of other countries in Asia. Although the total level of productivity in Iran is
still lower than Turkey, India and China, while we are doing better than all our
other neighbors, the rate of growth of our productivity has been excellent,
although it has slowed down in the last three years. We need to address this
slow down and correct it. In terms of quality, we need to improve but I think as
our level of productivity rises, so will the scientific quality.
In your view, what kind of efforts should
the Iranian universities, scientific institutions and organizations make in
order to attain the international position and authenticity they deserve for?
In every country, science is mainly a state
enterprise, most of the funding everywhere comes from the government. If we want
to improve our scientific standing in the world, we should ask our government
for better planning and more funding.
There are several issues to consider. One is that
scientific progress does not happen overnight, it takes time and patience on the
part of both the funding agency and the scientist. While the government should
made a long-term commitment to a steadily increasing level of funding, the
scientists should be given the level of job security they need to endure the
many years of effort it takes for a major discovery to be made.
This is both in terms of salary levels that
should be sufficiently high to retain the scientists in the workforce and
prevent them from going into carpet business!
And also in terms of long-term stability of their
jobs, Scientists should feel that their jobs are extremely secure, and they will
lose their jobs only if they are not productive scientifically. Although it goes
without saying, meritocracy is pivotal as the basis for employment should be
scientific credentials and nothing else. The government can encourage the
development of the required infrastructure. For instance, the level of chemistry
research is very high in Iran; we clearly have many good chemists. Why do we
need to import chemicals and reagents? Why not encourage these chemists to start
companies and support the needs of the Iranian scientific community? Finally,
something else that is sorely lacking in Iran is a spirit of collaboration and
Sharing expensive equipment and reagents is a
must, even labs in Harvard share! Sometimes during my visits to Iranian
universities I hear from doctoral students that although the neighboring lab has
such and such equipment that they need, they are not allowed to use it which is
unacceptable. Self-sufficiency is also important. We should note that not
everything should be bought from abroad. Many expensive reagents are easy to
make but unfortunately I hear about these reagents being ordered from abroad,
which is a waste of money and time.
About: This interview was conducted by
Ahmadreza Tavassoli, Iranian
freelance journalist and interviewer, with the help of his journalist friend,
Kourosh Ziabari, who is a member of Stony Brook University Publications'
editorial team and also a member of Finland's Ovi Magazine board of writers.
... Payvand News - 12/26/08 ... --