The human genome project
More than in any other field, innovations in the field of genetics herald the beginning
of a new era in medicine. Even now questions are asked about how these innovations
will change our life and health, and the diagnosis, treatment, and moreover the
prevention of disease. The completion of the project of decoding the human genome
has enormous practical meaning for each and every one of us that is of far greater
significance than man's historic first steps on the moon. The decoding of the genetic
sequence, together with new technologies such as genetic chips, will enable the
rapid, revolutionary development of drugs that can be tailored to each patient individually.
How will these developments be integrated ethically and how do we expect to cope
with the social and legal difficulties involved? Will these innovations result in
an increase in the gap between the populations of the rich and the poor countries
and between the rich and the poor in each society? It can be assumed that these
questions, which are already being asked today, will gain momentum at a more rapid
pace than previously thought.
The dramatic declaration of the completion of the decoding of the human genetic
sequence has, as expected, caused great excitement throughout the world and has
unleashed the potential of the human imagination with no little enthusiasm. While
the President of the USA compares the project to man's first step on the moon, the
media has been filled with a great many interviews and revelations about the moral
dangers inherent in this discovery. The practical significance of the completion
of the project and its actual relevance for each of us in general and the medical
profession in particular has been talked about less.
The decoding of the genome has also been accompanied by significant technological
progress, including the development of improved equipment, and the combination of
these will enable advances to be made in the development of drugs for diseases currently
The decoding of the sequence reveals genetic variation between humans. Molecular
genetic research is relatively young, having started only about 30 years ago with
little information about the structure of the genetic material. Today, three decades
later, amazing progress has been made, and we now know the full sequence of all
the genetic material in man and in a large number of other animals.
The innovation is thus the deciphering of the sequence of our genetic material.
People are similar to one another in 99.9% of their genetic sequences - the differences
between them are caused by variations in the structure of only 0.1% of their genes,
and this is the reason that some people have higher tendencies and some lower tendencies
to contract various diseases, develop side effects to certain drugs, etc. Technological
development has enabled us to understand the meaning of the millions of bases (represented
by letters) in the genetic code that constitute the basis for each individual's
tendency to contract certain diseases.
These important variations are currently being studied intensively, and this research
is still in its infancy. With regard to medical applications, there are 3 main types
of variations in the genetic material, as will be specified below.
The significance of genetic variation
"First degree variation" is present in a large proportion of the genetic material.
There are widespread regions that separate genes from one another - these are called
"junk DNA". They are repetitive sequences that are of research importance, but genetic
differences in these regions have no medical significance. They are used for other
purposes, such as paternity testing, identifying remains of victims, and for other
"Second degree variation" refers to genetic mutations that cause severe congenital
diseases such as Tay Sachs
disease and cystic fibrosis,
where prenatal diagnosis is extremely important. People carrying this type of mutation
are at risk of having an affected child if they marry a carrier of a mutation in
the same gene.
Tests are already available today for identifying carriers of some severe genetic
diseases, but the number of diseases for which this is possible is still limited.
Considering that there are thousands of severe genetic diseases that we would like
to be able to detect in the fetus and/or in the parents, it can be assumed that
in the near future there will be a battery of tests for identifying the carrier
status for severe genetic mutations. These will allow ascertainment of the parents'
carrier status and enable fetal diagnosis by amniocentesis. Such a test battery will be affordable
and quick, and will become a routine tool for gynecologists and geneticists.
"Third degree variation" is the most interesting type. The completion of the research
into this type of variation is currently the ultimate goal of all physicians and
patients because it is this that determines which common diseases each of us may
develop, such as diabetes, hypertension
various forms of
cancer, cardiovascular disease, etc.
Genetic structure and common disease
We shall now focus on third degree variation. These differences are responsible
for the predisposition of one individual to one particular disease and of another
individual to another. Furthermore, they are also responsible for the degree of
effectiveness of the person's response to medication. The fact that a particular
treatment is effective in only 60% of patients, for example, is explained by variation
in genetic structure, and this also accounts for the fact that different people
taking the same drug have different side effects.
Now that the entire genetic sequence has been decoded, the major research currently
underway is aimed at learning more about the genetic variations. An outcome of this
will be the preparation of batteries for examining the millions of bases, mutations
of which result in the development of common diseases. Within a decade or so, physicians
will be able to advise their patients on the most suitable environments for them,
and on what vitamins and minerals they should be taking in order to reduce their
risks for becoming ill. They will be able to determine which follow-up tests are
the most important, and, most interestingly of all, whether the person will develop
an illness. The physician will also be able to prescribe the drug most suitable
for the patient's genetic constitution in terms of both therapeutic efficacy and
the absence of side effects. Essentially, these are the tasks that we shall be facing
in the next ten years.
New beginnings in genetic technology
Alongside the decoding of the genetic sequence, there have also been highly significant
technological advances. Today, "genetic chips" that allow the simultaneous examination
of a very large number of genes have already been developed.
Apart from the identification of these genetic changes, the genetic chip also allows
us to learn about and identify functional changes in each tissue. The genetic chip
apparatus is relatively small. DNA segments that
are part of the subject's genes are smeared onto a glass slide, and in the near
future, it will be possible to examine a segment that is representative of all of
a person's genes. Using such a chip, the expressed genes (active genes that are
transcribed to RNA, which is later translated into protein) in a given tissue that
is being tested will be identifiable. In this way, RNA may be taken from both diseased
and healthy tissue, each stained with a different colored dye, and these poured
onto a chip in order to obtain the profile of the differences in genetic activity
between the two cells. By doing this it will be possible to see what is wrong with
the abnormal cell, and once this has been defined, 100 different drugs may be tested
to see which will lead to the restoration of the cell's normal activity.
Shortening the time for the development of drugs and adapting them for the patient
The combination of advanced technologies (such as the genetic chip) and the identification
of the sequence of the genes have already allowed pharmaceutical companies to shorten
significantly the time required to develop new drugs. Testing these can be carried
out without delay, and in the near future it will be possible to determine their
efficacy within weeks, without the need to experiment for years on animals and then
Concurrently, two very significant processes are taking place. The rate of development
of new drugs is about to improve strikingly, while individual tailoring of drugs
to each person on the basis of his genetic constitution will become feasible.
We should be aware that a certain time would have to elapse before we will feel
that the new technology is safe. We are currently at a stage when we are still digesting
all the developments that have taken place up to now. However, it is expected that
within 10 - 20 years, this will be the conventional way of developing new drugs.
What else does the future hold?
Apart from the anticipated advances in the fields of genetic testing and clinical
diagnosis, treatment and prevention of common, chronic illnesses, further achievements
resulting from technological developments in genetics can be expected. With the
advent of the genetic chip and the ability to identify all the differences and variations
in the genetic activity of each tissue, researchers predict that in another two
decades or so genetic diagnosis will be performed by monitoring serial blood samples.
Each person will be able to undergo a blood test once every 3 months, and the activity
of the RNA will be compared to that measured in the sample given 3 months earlier.
Any change will indicate the existence of a clinical finding. Using this method,
the physician will be able to diagnose some cases of cancer within a few weeks of
the onset, unlike today when a cancerous mass is usually detected only after a number
of years. This will be a highly significant achievement with regard to future therapy,
both for cancer and also for other conditions.
It is predicted that in 30 years clinical studies will not be conducted on humans.
Through computer imagery it will be possible to calculate and analyze the effect
of each drug (even a new, untried one) on the health of a particular person whose
genetic constitution is known, and to compare this with the effect of the material
on a person with a different genetic constitution.
Another result of these developments is a predicted significant increase in the
number of pregnancies resulting from in vitro (outside of the body) fertilization,
since it will be possible to guarantee a healthier fetus without performing an excessive
number of abortions. As the number of parameters tested in order to select the healthiest
out of a number of zygotes created by in vitro fertilization increases, this type
of fertilization will eventually be preferred medically to spontaneous pregnancy.
At the present time, the introduction of genes into a zygote is strictly forbidden
because of the fear of causing unexpected developmental defects in the fetus. However,
according to reports from leading world research centers, it appears that this will
in the future be a safe procedure, and within 20 years such treatments will be approved
for use and considered ethical.
The ability to use genetic treatments to cure genetic diseases will improve markedly.
These are currently given only in special cases, but their use will undoubtedly
It can be expected that the aging mechanism will be elucidated, and then, it can
be assumed, treatment of the zygote for the purpose of extending life expectancy
and possibly extending our "youth" will start to be carried out.
Alongside these developments, there will also be new ethical and legal problems
that will constitute new challenges for the general public. Physicians will have
to change their work methods since a considerable amount of their work will be in
the genetic field. They will have to integrate into a world of medicine that will
become even more mechanized than it is at present.
From the social and public viewpoints, it can be expected that anti-technological
movements will be established. There will be considerable social transformations
and the percentage of older people will increase significantly. The differences
in the ability to obtain assistance from new technology will lead to large social
gaps in each society and between different countries and continents. These are important
issues that will require careful consideration by the appropriate people in modern