Talking One Genetic Language; 
The Need for a National Biotechnology Information Center 
Biotechnology: New 
Genetic Miracles 
Because of Biotechnology, a term 
coined less than five years ago: 
• A man with diabetes is thriving on a 
new, life sustaining medicine. He had 
had a serious, potentially fatal, 
allergic reaction to various forms of 
insulin (traditionally extracted from a 
beef or pork pancreas). 
Now he is being treated with pure 
human insulin, manufactured not in 
the body, but in the laboratory. To 
make it, scientists inserted “good” 
human insulin genes into fast grow- 
ing bacteria, which then churned out 
great quantities of insulin hormone, 
• New hope has come to a woman 
with hairy cell leukemia, a rare 
cancer. Her doctors are giving her in- 
fusions of alpha interferon, another 
new substance manufactured in the 
laboratory by splicing genes into 
bacteria. The results are amazing: the 
leukemia is simply disappearing. 
And tumors in the bodies of over 
50 patients—including lung and 
colon tumors notoriously resistant to 
conventional therapies—shrank by at 
least half when they were treated 
experimentally, with “interleukin 2.” 
This genetically engineered substance 
turns the body’s white blood cells— 
often in short supply—into special- 
ized cancer killing cells, 
• Thick mucous clogs the little boy’s 
lungs. The doctors suspect cystic 
fibrosis but hesitate to start difficult 
therapies until they are sure of their 
diagnosis. Geneticists are called in to 
do a probe. By mixing a sample of 
the boy’s blood with a piece of DNA 
(deoxyribonucleic acid) they deter- 
mine that a crucial gene is missing. 
The test is positive; the diagnosis is 
made; antibiotic and other treatment 
can begin. 
What matters is the arrangement of 
these chemicals, or their exact se- 
quence in various combinations, along 
the backbone of the DNA molecule. 
For if the four different DNA bases are 
the letters of nature’s alphabet, the 
chemicals’ arrangement in groups of 
three is a sort of genetic code—dots 
and dashes that spell out all the in- 
structions the body needs to manufac- 
ture the myraids of proteins which 
build our bones, our muscles, the 
enzymes which catalyze our metabolic 
processes, and all in all make us human 
beings marvelously different individuals. 
If researchers can read and under- 
stand the language of heredity—if they 
can learn the sequence of bases in a 
gene—they can determine the makeup 
of the protein for which the gene is 
the blueprint. And they can clone that 
protein outside the body. Or find out 
why certain genes are switched on, or 
off during a lifetime. Or which ones 
are defective, or even missing. 
When scientists first began translating 
genetic messages, they had a difficult 
time. But in the past few years, they 
have gained powerful new automated 
tools with which to decipher and 
analyze, or sequence the messages of 
heredity. And they have developed 
ways systematically to change DNA and 
other important molecules, that is to 
manufacture new genes and perhaps 
repair defective ones, As they have 
Biotechnology: Roots 
New natural drugs and vaccines. Life 
saving therapies. Pain-saving 
interventions. 
All these are the result of Biotech- 
nology-research and development in- 
volving the all important molecules that 
control our life processes—how our 
bodies grow, how we age, whether we 
suffer a host of mental and physical 
diseases. Its central focus is DNA, the 
long, twisted threads in the nucleus of 
each of our ten trillion cells. 
Scientists have known for some 
thirty years that genes are essentially 
pieces, or chemical subunits, of DNA 
carrying the messages of heredity in 
the strands of the famous double helix. 
A string of thousands of these units, 
which themselves are groups of atoms 
composed of four different nucleotide 
bases—A (adenine), T (thymine), C 
(cytosine), and G (guanine)—makes up 
a gene. 
US. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • National Institutes of Health 2 
done so the sciences of molecular 
biology and molecular genetics have 
become Biotechnology. 
All this effort, all this information 
would be useless without computeriza- 
tion. There is no way even an Einstein 
could analyze, store or manage it with 
a pencil and a human brain. As infor- 
mation has poured out of the 
laboratories, factual research data bases 
have been developed to store it, There 
are now about a dozen such data bases, 
set up for the most part by researchers 
with an avocational interest in com- 
puters. The chart on the next page 
describes these data bases. 
For scientists depend on the data 
bases actually to accomplish their 
research. They must tap into a base like 
GenBank to find matching sequences. 
For example, they had known for a 
decade or so that oncogenes transform 
normal cells into cancer cells. Wonder- 
ing why Nature would put the seeds of 
our own possible destruction within us 
they searched the data bases and 
discovered that the oncogene 
sequences matched those of a normal 
human growth gene. This suggests that 
cancer may be caused by a normal 
gene being switched on at the wrong 
time. And that they might some day 
find a way to switch it off. 
But the different data bases use dif- 
ferent information systems—different 
computer languages, and these have 
resulted in a veritable Tower of Babel. 
No scientist in the world can know 
enough about each of these computer 
systems to tap into all of them, 
Even if such a genius appeared, the 
data bases lag so far behind that he or 
she might miss a discovery already 
made. And society might miss a new 
drug like Captoril, which controls high 
blood pressure—designed by knowing 
what a molecular target in the body 
looks like, and synthesizing a molecule 
that attaches to that target. Or a just- 
announced test that uses genetic 
material to detect the AIDS virus in 
blood samples. 
How Biotechnology 
Information is Unique 
The complexity and size of 
Biotechnology information astound the 
imagination and make it different from 
other scientific information. And this 
information is growing today at an 
amazing rate. 
Within every one of us, tens of 
thousands of individual human genes 
control special life processes. Three 
billion units of DNA make up the 
human genome (all human genes taken 
together), and only .01% of them have 
been sequenced. With current 
technology, sequencing these three 
billion units could consume 30,000 
person-years and upward of $2 billion. 
Fortunately, current technology does 
not stand still. 
Technical advances—including ways 
to separate large molecules and indi- 
vidual chromosomes—have upped the 
rate of analysis about ten times in the 
last decade. A molecular biologist at a 
technically advanced laboratory today 
can sequence about 300 DNA units a 
day. And now scientists at CalTech have 
reported the successful development of 
an automatic DNA sequencing machine 
that again speeds sequencing tenfold 
(and cuts the cost for each base in 
half—from one dollar to fifty cents). 
The Biotechnology 
Information Gap 
The problem is simply stated but hard 
to solve. The data bases are swamped. 
Take the best known, GenBank, set up 
under contract by NIH and co-funded 
by a number of Federal agencies. By 
mid-1986, only 54% of the data 
published in 1985 had made it into the 
data base. 
This is because the rate of publica- 
tion has grown so rapidly—from one 
sequence composed of 76 bases in 
1965 to a total of 11,552 sequences 
composed of 9,924,741 bases by 1986. 
The contents of GenBank by year of 
publication are in the table on page 4. 
What is at stake here is not merely 
the convenience of researchers search- 
ing for scientific papers. What is at 
stake is the progress of Biotechnology 
around the world—our understanding 
of life at a molecular level and hence 
our knowledge of health and disease. 3 
BIOLOGY KNOWLEDGE BASES 
Needed: a National 
Biotechnology 
Information Center 
The whole biotechnological information 
system is so overloaded that there is a 
danger scientific progress may grind to 
a halt. To prevent that from happening, 
and to move the field along faster, we 
need a central repository for storing 
and sharing the information resulting 
from genetic research. With this 
problem in mind, Rep. Claude Pepper 
introduced a bill (H.R. 5271, 99th 
Congress; reintroduced in the 100th 
Congress as H.R. 393) to create a 
National Biotechnology Information 
Center, at the National Library of 
Medicine. 
Working with the laboratories from 
which information comes, experts at 
such a center would seek to coordinate 
data as it is accumulated—to store, 
process and make it available to the 
research community, nationwide. 
At such a center, too, computer 
scientists—with the help of some of 
the world’s outstanding molecular 
researchers working next door at 
NIH—would create new computer 
information systems so that investigators 
throughout the country could ask ques- 
tions and get answers quickly. They 
would encourage consistent ter- 
minology for researchers and data bases 
so that research results entered into 
computer systems could be shared and 
be made widely available. 
Cells and Tissues 
ATCC Cell/Tumor Bank 
Hybridoma Data Bank 
Cell/Tissue Protein Arrays 
Proteus Technologies, Inc. 
Protein Databases, Inc. 
Chromosome Libraries 
Los Alamos/Livermore Banks 
Cytogenetic Maps 
Cytogenetics Database 
Genetic Maps 
Human Gene Library (Yale) 
Human Gene Map (SHG) 
Mouse Map (Jackson Labs) 
Genetic Maps (NIH) 
Restriction Maps 
Genetic Maps (NIH) 
— Gene Maps 
Genetic Maps (NIH) 
DNA Sequences 
GenBank (NIH) 
EMBL Bank (Europe) 
mRNA Sequences 
Gen Bank (NIH) 
EMBL Bank (Europe) 
Protein Sequences 
Protein Resource (NBRF) 
Japan Protein Bank 
Protein Structures 
Brookhaven X-Ray Databank 
Crystallographic Data Centre 
Mutagens/Carcinogens & Drugs: 
Interaction with DNA & Proteins 4 
In the new information systems, 
research would be stored in such a 
way that data retrieved from one 
source could be linked to other related 
findings, and to other research data 
bases. So investigators could ask one 
computer a question and that computer 
would automatically search for the 
answer not only in its own knowledge 
base but in other research bases as 
well. 
GenBank Contents by Selected Year of Publication 
(as of August 1986) 
Year 
Bases 
Sequences 
Av Seq Len 
% of Published 
1965 
* 
76 
1 
76 
1970 
* 
249 
3 
83 
1975 
* 
6,160 
54 
114 
1980 
* 
439,717 
852 
516 
90 
1983 
1,929,368 
1,630 
717 
80 
1984 
2,569,480 
2,475 
1,038 
75 
1985 
2,329,394 
1,957 
1,190 
54 
1986 
290,708 
161 
1,806 
4 
Total 
(1965-1986) 
9,924,741 
11,552 
859 
82 
Why an Information 
Center at the National 
Library of Medicine? 
Developing such a national center at 
the Library would, of course, prevent 
duplication. It would enable scientists 
to work in a more collaborative 
style—conferring frequently to avoid 
reinventing the wheel. 
Most important, it would give 
researchers the means they need to do 
their job. Now each of them is essen- 
tially alone, working on his or her own 
piece of the genome puzzle. What they 
need is something they cannot get in 
any regional or university center: a 
national “board” on which they can fit 
that incredibly complex puzzle together. 
Starting a national center at the 
Library would be a cost effective, 
logical move. For it would build on the 
unquestioned leadership of the library 
in biomedical information. Nor would 
it be necessary to build a new facility, 
or to invest in extensive computer 
equipment to get fast results. 
This is because the Library is already 
deeply involved with the communica- 
tion of biotechnology research findings, 
through its biomedical literature and 
computer data bases. Over 97% of all 
published research containing DNA se- 
quences can already be found among 
the 6 million references in the 
MEDLINE (MEDical literature onLINE) 
system. The Library has twenty-two 
years of experience in building and 
maintaining large computer files for 
biomedical researchers and health care 
professionals. 
Many of the tools and techniques 
developed by the Library to classify in- 
formation and biomedical literature can 
be applied to the understanding of the 
language of molecules. For example, the 
computer methods used to search for 
matching words and phrases in the 
medical literature can be applied 
directly to the finding of matching pat- 
terns of molecules in different DNA 
gene sequences. 
The Payoffs: Toward 
Better Health and 
Less Disease 
The functions proposed for the 
National Biotechnology Information 
Center seem to be absolutely necessary 
to do the genetic research job that has 
to be done in the years ahead. 
We need such a Center to prevent 
duplication and to get more bang for 
our research bucks. We need it to fit 5 
together the pieces of the genetic puz- 
zle and acquire the knowledge that 
would benefit humankind in many 
ways. 
With such knowledge, we could 
develop deeper understanding of the 
root causes of diseases that still plague 
us. This is true of diseases we know 
are inherited, of course, like Sickle Cell 
Anemia or Thalassemia. 
But scientists feel that our likelihood 
of falling victim to the common and 
serious diseases, like heart disease, 
cancer, and arthritis, may well be in- 
flux need in complicated ways by the 
workings of our genes. Researchers aim 
now to learn more about these genes, 
and their relation to each other. 
From this deeper understanding 
would come exciting new cures and 
interventions: 
• New vaccines to prevent diseases and 
newer and more effective drugs to 
treat them; 
• Gene therapy to cure even pre- 
viously fatal disorders; 
• Early warning for such diseases as 
Huntington’s Chorea; 
• Control of such dreaded conditions 
as Alzheimer’s Disease; 
• Better health generally through more 
plentiful food supplies—-gained by 
inserting genes to make new plant 
species resistant to insects and 
herbicides. 
Down the road a bit we can envision a 
scenario like this: 
A single defective gene has left a 
little girl with a horrible immunological 
disorder called ADA (Adenosine 
Deaminase Deficiency). She is 
emaciated, and racked with pain. 
Because her body has absolutely no 
defenses against infection, she has had 
pneumonia almost all her life. Similar, 
luckier, patients have been helped by 
transfusions from a brother or sister’s 
bone marrow that could be matched 
with their own. But only 3 out of 10 
patients have such siblings, and this girl 
is not one of them. 
Now this patient is about to receive 
an exciting form of gene therapy. 
Building on successful research results, 
the doctors plan to insert a normal 
gene into her bone marrow cells. They 
believe this treatment will produce an 
enzyme to correct her condition, and 
cure her. 
Another scenario: A vigorous young 
man has developed a cancer of the 
lymph nodes. A genetic probe shows 
that the disease is due to the switching 
on of an oncogene in his body. Doc- 
tors inject a medicine containing a 
repressor molecule, and this switches 
the oncogene off. He recovers 
immediately. 
Such miracles, such real cures, are 
expected from biotechnology research. 
This is the work the National 
Biotechnology Information Center is to 
assist. NATIONAL LIBRARY OF MEDICINE 
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