Possibly opening a new era in human biology and medicine,
and certainly creating many pressing questions and
controversial issues, two competing teams of researchers and
scientists presented their first interpretations of the
human genome, the set of DNA-encoded instructions that
specify a person.
The Human Genome Project (HGP), an international goverment-
funded research effort, and Celera Genomics, a private
research group, are aiming to create detailed genetic and
physical maps of the human genome, to determine the complete
nucleotide sequence of human DNA, to localize the estimated
30,000-100,000 genes within the human genome, and to perform
similar analyses on the genomes of several other organisms
used extensively in research laboratories as model systems,
as well as to examine the ethical, legal, and social
implications of human genetics research.
Also on the HGP's agenda is to train scientists who will be
able to utilize the tools and resources developed through
the research to pursue biological studies that will improve
human health.
The interpretation of the genome -- identifying the genes,
their functions and controls, and how they relate to human
physiology and disease -- is expected in time to
revolutionize medicine by clarifying the mechanism of many
diseases and generating new tests and treatments. However,
it raises a far greater moral issue: who are we, mere
mortals, to tamper with human genes?
The HGP realized that this question would nag at the minds
of many, as the use of such genetic knowledge would have
strong implications for both individuals and society and
would pose a number of policy choices for public and
professional deliberation. They have, therefore, included an
analysis of the ethical, legal, and social implications of
genetic knowledge, and the development of policy options for
public consideration are another major component of the
human genome research effort.
The issues involved in decoding the human genome became
public in the mid-1980s, with the formation of the HGP and
gained much press coverage and scientific analyses.
The Department of Energy (DOE) initially, and the National
Institutes of Health (NIH) soon thereafter, were the main
research agencies within the U.S. government responsible for
developing and planning the project. By 1988, the two
agencies formally combined efforts in the human genome
research. In 1990, they published a joint research plan,
"Understanding Our Genetic Inheritance: The U.S. Human
Genome Project. The First Five Years FY 1991-1995."
Today, the HGP is a consortium of academic centers, mostly
in the United States and Britain but with members in France,
Germany, China and Japan. The U.S. National Institutes of
Health and the Wellcome Trust of London are the main
financers of the consortium.
Another research group has since been founded, however this
one is privately run. Each team is highly critical of the
other's approach, vying for the recognition as the most
accurate decoder of the human genome. But the competition
has proved enormously beneficial overall.
The government consortium was on a leisurely track to finish
the genome by 2005 until Dr. J. Craig Venter, president of
Celera Genomics, in Rockville, Md., a privately-run group of
researchers and scientists, jumped into the race in May
1998, saying he would complete the genome by 2000. Now each
group is fighting to be the first to clinch the discovery
and present the data to the public at large.
Since last June, however, both have been observing a limited
truce. On June 26 last year, when each side had finished
assembling its version of the genome, a pact was made at the
White House, calling for joint publication of their
findings.
This "joint publication," which each side published in
competing scientific journals in different continents,
disclosed years of research to the public just last week.
The HGP's version of the human genome is described in a 62-
page series of scientific papers in the February 15, 2001,
issue of Nature, a London based magazine. The
principal author is Dr. Eric Lander of the Whitehead
Institute in Cambridge, Massachusetts.
Celera Genomics published their report in a 48-page article
in Science, based in Washington.
Physically, the genome is minuscule -- two copies of it are
packed into the nucleus of every ordinary human cell, each
one of which is about a fifth the size of the smallest speck
of dust the eye can see. But the genome is vast in terms of
its informational content. Composed of chemical symbols
designated by a four-letter alphabet of sugars -- A's, T's,
C's, and G's -- the human genome is some 3.2 billion letters
in length. If printed in standard type, it would cover over
150,000 pages of this newspaper.
The enormous task of decoding the genomic message began in
1990 and is now substantially complete, although both teams'
versions of the genome are riddled with gaps.
Despite the two team's many differences, they largely agree
on their findings about the human genome. Theirs is the
first overall look at a genetic document of extraordinary
strangeness and complexity. No one expected it to be
comprehensible at first glance and the two teams have so far
mapped only the principal features of its terrain.
The teams have uncovered much interesting data about the
human genome. Celera Genomics has compiled a parts list of
the proteins needed to make a person. The other team has
discovered that human genes seem to have been derived
directly from bacteria.
In a news conference on February 10th in Washington, the
teams discussed their findings, confirming other oddities,
too. They postulate that most of the repetitive DNA
sequences in the 75 percent of the genome that is apparently
useless ceased to accumulate many years ago, but a few of
sequences, namely one specific family of repetitive DNA
situated close to the core of the active genes, are still
active and may do some good.
Their main discovery is how few human genes there seem to
be. The number of human genes has long been thought to be
around 100,000, but with the sequence of human DNA units in
hand the two teams have found far fewer than expected. Dr.
Venter says he has identified 26,588 protein-coding genes
for sure and another 12,000 possible genes. The consortium
says there are 30,000 to 40,000 human genes. Both sides
favor the lower end of their range, since their methods of
gene discovery tend to predict more genes than they believe
exist.
The low number of human genes -- say 30,000 -- can be seen
as good for medicine because it means there are fewer genes
to understand.
However, this discovery reveals that the human genes don't
number that much more than the roundworm's. The laboratory
roundworm, sequenced in December 1998, has 19,098 genes and
the fruit fly, decoded last March, owns 13,601 genes.
The roundworm, a minuscule creature that infests the
intestines of humans and some animals, has a body of a total
of 959 cells, of which 302 are neurons comprising its brain.
Humans have 100 trillion cells in their body, including 100
billion brain cells.
Both teams discuss various possible solutions of how it can
be that though people don't have all that many more genes
than these simple creatures, yet they are, nonetheless, so
much more complex.
Dr. Venter said he could find only 300 human genes that had
no recognizable counterpart in the mouse. He then went on to
deduce and speculate that the chimpanzee would have an
almost identical set of genes as people, but possess variant
forms of these genes.
Dr. William Haseltine, president of Human Genome Sciences,
would not change his long-standing opinion that there are
120,000 or so human genes. Dr. Randy Scott, chief scientific
officer of Incyte Genomics, predicted in September 1999 that
there were 142,634 human genes. Last week, however, Dr.
Scott said he accepted the rationale for the smaller
number.
Dr. Haseltine, however, said last week that his company had
captured and sequenced 90,000 full-length genes, removed all
usual sources of possible confusion and he has made and
tested the proteins from 10,000 of these genes. He believes
that both research groups reached that low estimate through
faulty methods.
Regardless of the number of genes a person body has, knowing
how to recreate them can lead to drastic results. Dr. J.
Craig Venter, president of Celera Genomics, concludes his
article about the human genome with a warning against what
he sees as the dangers of determinism, "the idea that all
characteristics of the person are `hard-wired' by the
genome." Dr. Francis Collins, leader of the public
consortium and Celera's rival, said last week that "one of
the greatest risks of this focus on the genome" is that
people will draw the conclusion that their choices in life
are "hard-wired into our DNA and free will goes out the
window and we move into this mindset of genetic
determinism."
It's easy to refute the advocates of genetic determinism, if
any staunch ones exist, because it is obvious to scientists
that human behavior is not completely specified by the
genome. But the opposite position -- that biology has in no
way shaped human behavior -- seems equally implausible.
Dr. Plomin, who discovered the first gene that affects human
intelligence, describes the influence of genes on human
behavior as "probabilistic rather than deterministic."
Another expert said that nature has found it more effective
to set loose prescriptions -- epigenetic rules, he calls
them -- to guide those trying to survive in complex and
hazardous jungle of human society.
When fully decoded, the human genome will have the potential
to be the undeniable guide of both the good and bad side of
human nature, which can manifest themselves in the creations
and cruelties of the human mind.
Both teams' versions of the genome now seem to be in a good
enough state to be of great use to biologists. The
consortium's genome is available for free and Celera's
through subscription. But Celera provides extra services,
such as the ability to compare the human genome sequence
with that of the mouse. Mouse DNA has retained a very
similar sequence to human DNA both in its genes and in the
DNA regions that control the activity of genes, but has
diverged through mutation in all the nonessential parts of
the genome.
The consortium, however, is also working on the mouse genome
And plans to have that, as well as other important tools,
available to the public.
Though both teams research is not yet complete and show many
gaps in to genome's makeup, Dr. Venter included a comparison
chart in his article that places his group in a more
favorable light. According to his chart, the consortium's
version of the genome has many more gaps than Celera's and
the gaps are larger. But in an interview Dr. Venter
complimented the consortium's efforts. "We are really
impressed at how good the public paper is, given their input
data," he said.
Dr. Lander rebutted this attack, saying Celera's strategy
was a grand experiment that failed because it produced more
than 100,000 assembled pieces that could not be attached to
the genome sequence. Dr. Mark Adams of Celera returned that
the company had assembled more than 95 percent of the genome
into 2,845 large pieces and those were well anchored to the
genome.
Disregarding their fierce competitiveness, both teams used
information the other teams had uncovered. Dr. Venter used
not only the snippets of DNA decoded by the consortium but
also important information about their position generated by
Dr. Robert H. Waterston of Washington University in St.
Louis. The consortium copied Dr. Venter's method of linking
DNA sequence data by "paired-end reads," and his reliance on
heavy-duty computing to assemble data.
Experts are likely to debate which team's method for
sequencing the human genome is better. But after all is said
and done, which the scientists hope will be in the near
future, the deep moral issues that are just up for
discussion now will be on the forefront of every thinking
person's mind. Unfortunately, for most people, these
questions don't have definite answers and, like the
frightening option of being able to choose to continue one's
life or end it, the choice of creating a whole new life may
become a commonplace decision.
