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Human Genome makes
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Case Study Summary
Biotech and genetic research promises to yield huge benefits to society in the
Genetic researchers are looking
future while becoming a multimillion-dollar industry. The three USA TODAY
forward to medical miracles — and articles in this case study present recent scientific progress and the challenging
backward into evolutionary history questions it is generating. Technology has the potential to redefine the moral
landscape. Will it? This is an important topic of discussion for current and future
members of business, political, medical, legal and scientific communities.
By Steve Sternberg
DNA-rights defenders:
Get off my genetic property
Money creates conflict of research
vs. privacy
By Elizabeth Neus
Thinkers: ‘Genes
cannot explain’
‘No evidence of 30,000 genes
evolving over. . .tens of millions of
years can tell the whole story.’
By Greg Barrett
Case Study Expert:
Janis Smith
Adjunct Professor,
Brown University
USA TODAY Snapshots®
Genetically altered food:
Women more skeptical
Women
71%
59%
50%
47%
37%
Would eat
such food
Source: www.pulse.org
Men
35%
Would give Willing to
it to their pay more for
children
non-altered
food
By Lori Joseph, and Sam Ward, USA TODAY
Cover story
Human genome makes
mind-boggling reading
Genetic researchers are looking forward to medical
miracles — and backward into evolutionary history
By Steve Sternberg
USA TODAY
The first close reading of the “The
Book of Life” — the 3 billion letters that
make up the human genetic code —
reveals that it’s packed with more
mysteries and surprises than a pulp
thriller.
Perhaps the biggest surprise since the
code was deciphered in June is that it
takes just 30,000 to 40,000 genes to
make, maintain and repair a human.
That’s far fewer than the 140,000 genes
that some had predicted and not many
more than a worm or a common weed.
“If you’re judging the complexity of
an organism by the number of genes it
has, we’ve just taken a big hit in the
pride department,” says the National
Genome Research Institute’s director,
Francis Collins, who also heads the U.S.
arm of the international Human
Genome Project (HGP).
Twin analyses of the genome were
released today by two leading journals,
Nature and Science. Both issues also are
packed with reports looking at what the
genome tells us about ourselves and how
we differ from other organisms on Earth.
And the genome is the perfect place
to look. If ancient Greeks talked of the
“Great Chain of Being,” the genome is
it, and in a form that the ancients could
hardly have imagined — a spiraling
chain of chemicals running through
every living being. In humans, the chain
is vast, “25 times larger than any
previously studied genome and eight
times larger than the sum of all such
genomes,” Collins reports.
Among the findings:
uMen, whose sperm cells divide
almost endlessly to boost opportunities
for fertilization, are twice as likely as
women to generate abrupt genetic
mutations. These altered sequences
may mingle with those of the mother’s
genes after fertilization, shuffling wild
cards into their child’s genetic
inheritance. Some errors may make no
difference to the developing fetus, some
might be beneficial, and some might be
harmful. What this means to human
development is poorly understood.
uProteins, the most complex large
molecules in nature, are much more
complicated in humans than in animals
or plants.
Reprinted with permission. All rights reserved.
AS SEEN IN USA TODAY LIFE SECTION, MONDAY, FEBRUARY 12, 2001
USA TODAY photo illustration: source/PhotoDisc
Reprinted with permission. All rights reserved.
uHundreds of human genes appear to have come from
bacteria millions of years ago. Whether the bacteria infected
humans or they were carried by a virus is still unknown.
uEvery human’s genome carries the residues of evolution,
a history stretching back millions of years.
The journals discuss these things and many more. Nature
begins with a 68-page report by the genome project, a
publicly funded consortium of 20 groups in the USA, United
Kingdom, Japan, France, Germany and China. Science offers a
48-page analysis by J. Craig Venter, CEO of Celera Genomics in
Rockville, Md., and an equally impressive who’s who of
collaborators worldwide. Celera is the private company that
spurred the public-private race to solve the genome to its
photo finish in June. Both groups have produced detailed
sequences covering over 90% of the genome. And both
versions agree on the rough number of genes in the genome,
the genome’s organization and other key features.
Multi-tasking genes
Probably the most intriguing question to emerge from
these analyses is this: How do relatively few genes build and
maintain an organism as complex as a human, with 90,000 to
300,000 proteins and 100 trillion highly specialized cells?
Venter, whose firm challenged the publicly funded
international sequencing project by exploiting a clever,
automated technique called “whole genome shotgun
sequencing,” says the answer promises to topple a hallowed
principle of the gene world: “one gene (makes) one protein.”
The new analyses indicate that each gene makes on average
two proteins. Somehow — the how is still being explored —
the cell’s machinery can order up the protein it needs at any
given instant, researchers say.
When that occurs, enzymes within the cell swing into
action. They splice together the genetic sequences that make
the needed protein, even when the sequences are in pieces,
spread out along the chromosome.
This means that the human genome is anything but a static
alphabet. It’s a living text that continually edits and rewrites
itself, spelling out biological messages necessary for survival.
“It’s a manuscript in flux,” says Eric Lander of the
Whitehead Institute Center for Genomic Research in
Cambridge, Mass., a lead researcher in the HGP. “It’s a neverending, constantly changing story.”
The substance of the manuscript is more astonishing yet, says
Venter. “It is a guidebook to the formation of our species.”
The genome also will serve as a guide for researchers who
are trying to develop new ways of treating cancer and other
ailments that have plagued humans. Knowing the identity
and location of genes, for instance, enables researchers to
study their patterns of expression — when they turn on and
off. These clues have already yielded useful information.
One report in Science, for instance, compares gene expression
in normal vs. cancerous tissue. Researchers found several genes
that were either “silenced” or over-active in breast and colon
cancer. If doctors can figure out what triggers these abnormal
genetic patterns, researchers say, they may be that much closer
to learning how to block them.
Putting the genome in order
Sequencing the genome involved placing in their precise
order the seemingly endless strings of nucleic acids that
make up therungs of the twisted, 6-foot ladder of DNA inside
every living cell. The nucleic acids are adenine, thymine,
cytosine and guanine. They are represented in the genome
sequence by the letters A, T, C and G.
Over half of the genome is rich in segments called repeats,
bits of sequence that appear over and over again, which offer
a remarkable window into evolutionary history.
“We can look at your DNA or mine,” says Kathy Hudson,
assistant director of the National Genome Research Institute,
“and see a history going back 800 million years.”
In the genome, says Douglas Wallace, director of molecular
medicine at Emory University in Atlanta, evolution is plain to
see.
Wallace says two lines of evolution converged in humans.
One is a set of genes from the first bacteria capable of living in
an oxygen-rich atmosphere, he says. The second set comes
from the single-celled organisms that gobbled up the bacteria
and co-opted their ability to turn oxygen into energy.
Genes from those bacteria still reside in the human genome,
the new analysis shows. Says Wallace: “We have the fusion of
two different lines of evolution into the same genome.”
When researchers speak of the genome, they’re really
talking about the sum of genetic sequences that make up the
23 pairs of chromosomes in each human cell, half of each pair
donated by a parent. But the new research indicates that this
genetic information isn’t evenly divided on the
chromosomes. Lander describes the genome as a
Book of life: A detail from a diagram of Chromosome 19 shows the complexity of the human genome.
“remarkably uneven landscape.”
“Some chromosomes are chockablock with genes, (and)
others are virtually devoid of genes,” Lander says. “The weirdest
chromosome in the genome is (number) 19. It’s chockablock full
of genes and other functional elements, far beyond what you’d
expect, given its measly size. It’s a mighty little chromosome
there. Given its size, it has grand aspirations.”
In contrast, he says, “chromosomes 4 and 8 barely pull
their weight.”
What genes lurk on chromosome 19? Among others: the
Apo-E gene, linked to Alzheimer’s disease; the LDL receptor
gene, linked to bad cholesterol and heart disease; and the
EpO gene, needed to form oxygen-carrying red blood cells.
There’s even a gene that has been linked to a sometimes
fatal, inherited reaction to anesthesia.
No one fully understands the laws that govern genome
function or how to manipulate the genes to treat human
disease. But genomics and biotech firms, often partnered with
major pharmaceutical firms, are determined to change that.
A biotech boom
Such research promises to yield huge benefits to patients
of the future — and possibly Nobel prizes to scientists who
developnew treatments or even cures. They’ll have plenty
to work with.
Researchers have already identified 1,100 genes with at
least one mutation that has been linked to disease. Biotech
firms are uniquely positioned to plunge into such research.
A biotech industry analysis, released late last month by
Lehman Brothers, asserts that the genomics revolution
will double biotech revenues to $4 billion annually by
2005. The best investments, it says, will be in newly
developing technologies.
One of those is the new multimillion-dollar industry that has
sprung up to catalogue what some call the human “proteome,”
the complete roster of proteins in the human body.
Proteins by the tens of thousands serve as workhorses in
every cell, performing functions necessary for life.
Not surprisingly, plenty of scientists and businessmen
want to get in on the action, despite market ambivalence
about many other high-tech enterprises.
“You only have to whisper the word proteomics,” says
Josh LaBaer of Harvard University’s Institute for Proteomics,
“and venture capitalists come knocking at your door.”
Other firms have begun collecting genetic information
from human volunteers — twins, if possible — so that
researchers can study how genes and proteins function in
both healthy people and those with deadly diseases. This
holds great promise.
“What will come out of this is a complete redefinition of
human biology,” says Paul Kelly, CEO of Gemini Genetics in
Cambridge, England.
Kelly’s firm has forged an agreement with Celera to help
the genomics firm look for common disease genes, such as
those for osteoporosis and diabetes. Where? In Gemini’s
populations of twins and other research cohorts in Canada,
the United Kingdom, New Zealand and Australia.
Celera also has begun moving into proteomics. Celera’s sister
company, Applied Biosystems (both are divisions of Applera
Corp.) has matched its breakthrough gene-sequencing device
with one that can speedily sequence proteins.
“Celera is making the biggest play in proteomics of
anybody,” says Venter. “We have $1.1 billion in cash in the
bank, and we’re building a facility where we can sequence a
million proteins a day.
“That’s driving our program for the discovery of new
diagnostics and therapeutics — particularly in cancer. We’re
betting that we can actually do something about cancer.”
“We are made of and by protein,” says Harvard’s LaBaer,
whose institute plans to obtain physical copies of every
human gene and to use those genes to create the hundreds
of thousands of proteins.
“Virtually every pharmaceutical today, from aspirin to
chemotherapy, works by affecting protein function,” LaBaer
says. “This is where the future of biology, and medicine, resides.”
AS SEEN IN USA TODAY LIFE SECTION, MONDAY, SEPTEMBER 25, 2000
Health and Science
DNA-rights defenders:
Get off my genetic property
Money creates
conflict of research
vs. privacy
By Elizabeth Neus
Gannett News Service
WASHINGTON — Who owns your DNA?
The answer might not be you.
In an era when the map of the human genome can
be accessed by any professor with an Internet
connection, the question becomes more crucial
every day. Courts and lawyers and legislatures
wrestle with it; people who joined medical studies
wonder just what their participation means.
Courts have ruled that people who donate actual
tissue — pieces of organs, tumors or blood, for
example — have no right to financial compensation
if a drug or treatment is developed from research
done on that tissue.
But DNA, which contains the
genetic blueprint from which you
were built, seems more
personal, something whose fate
you and you alone should have
the right to control.
Oregon is the site of the most
recent battle over the rights to
DNA. The state’s 1995 genetic
privacy law, one of the first in
the nation, gives a person
property rights to his or her own
DNA. A proposed change to the law
last year would have taken those rights
away. An advisory committee is expected to offer
recommendations to the Legislature and the
governor next month on how to proceed.
includes health histories, blood, tissue samples and DNA —
“There are many competing agendas here,” says Gregory will be used.
Fowler, executive director of Geneforum.org, an
“A lot of time and commitment and love have been
organization founded to educate people about gene-related poured into this (by the volunteers), and they’re concerned
issues. He also is a member of Oregon’s advisory committee. that the data isn’t exploited,” Paris says. “But we have to get
Experts have tried to sort out those agendas for years. over the fact that companies may make money (from the
This year the federal government strengthened its data). How do you do (research) without money?”
regulations protecting human research subjects, hoping to
John Kilyk Jr., managing partner with a Chicago law firm
make more explicit the process by which patients are told specializing in intellectual property, says that those who
what a study will entail.
believe volunteers should get a cut of any proceeds fail to
The National Bioethics Advisory Commission report on understand how much money goes into the research
which some of those recommendations were based noted upfront, compared with what’s earned at the other end.
the difficulty in protecting subjects no longer physically
“There is a lot of money at stake, or at least there’s perceived
involved in a study.
to be a lot more money at stake,” he says. “But there’s no
“Researchers are often unclear whether research on guarantee that (researchers are) going to find something …
human tissue makes the people from whom it came ‘human What (laypeople) don’t appreciate is the time and money
subjects,’ ” the commission
involved in getting to that
wrote President Clinton.
point, and the number of
In some cases, those who
winners and losers.”
donated the original tissue or
Andrews rejects that
DNA are dead, leaving wide
argument.
open the question of whether
“It’s an unnecessary windfall,”
new research can be done
she says. “They’re being
uwww.geneforum.org —
with that material — and who
rewarded disproportionately to
Geneforum
has rights to it.
what they do. It’s a trick on the
For example, 4,000 of the
public. It’s like patenting the
10,000 people who have
alphabet and charging people
uwww.framingham.com/heart —
taken part in the 52-year-old
every time they speak.”
Framingham Heart Study
Framingham Heart Study
Some companies have found
have died, and coordinators
a way to compensate those
uwww.bioethics.gov — National
of that study don’t know who
who volunteer DNA without
can give consent to use the
going into dollars and cents. A
Bioethics Advisory Commission.
information from the dead
company called DNA Sciences,
Click on “Reports” to find “Research
volunteers if the study
which wants to find geneInvolving Human Biological
becomes a commercial
based tests and treatments for
Materials: Ethical Issues and Policy.”
venture, as planned. They are
common illnesses, is building a
trying to work that out.
large database of DNA from
“We certainly feel we’re
scratch by asking volunteers to
uwww.dna.com — Gene Trust
blazing a trail here,” says
donate. If a relevant test or
Susan Paris, vice president for
treatment is found, any
university relations at Boston
volunteer who participated in
University, which runs the Framingham study.
that study will be offered the test or treatment free, says
The usual concerns also come into play when the issue is chief business officer Steven Lehrer. “The whole concept of
genetics. Researchers make every effort to disconnect the paying people for (taking part in) research is very negative,”
DNA samples from the identities of their donors, but he says. “It looks like you coerced them.”
experts still worry.
With the trend toward the creation and use of extremely
“No genetic sample can be totally anonymous,” says Lori large databases such as Framingham and DNA Sciences’
Andrews of the Institute for Science, Law and Technology at Gene Trust, “the property value of any individual genome
the Illinois Institute of Technology. “We use DNA in forensics gets smaller,” says Gillian Woollett, associate vice president
to identify people. I could always figure out who it is.”
for biologics and biotechnology at the Pharmaceutical
Complicating the issue further is money — lots of it.
Research and Manufacturers of America, a drug industry
Biotech and genomics companies have been hot in recent trade group.
years in the stock market, and even academic researchers, once
Besides, she says, what portion of your DNA is yours? The
seen as above the financial fray, often have start-up companies.
large part of the genome we share with chimpanzees? The
The federal government is balking at Framingham’s plans part you share with an identical twin?
to go commercial; Washington underwrites the famous
“Do you own what is unique to you,” she asks, “even if
study, which provided the base line for nearly everything you don’t know what’s unique to you?”
we know about heart disease. Some of the 6,000 living
participants are nervous about how their data — which
Click here
AS SEEN IN USA TODAY LIFE SECTION, MONDAY, FEBRUARY 12, 2001
Thinkers: ‘Genes
cannot explain’
By Greg Barrett
Gannett News Service
The philosopher, the theologian, the biologist and the
author of spirituality are in basic agreement on this:
Revelations released today about the human genome are
about as significant to our understanding of metaphysics as
walking on the moon is to our understanding of the
universe. A boundary we still cannot fathom.
That is to say, this evolving map of our genes is not likely
to sway matters of the spirit. Never mind the project’s
findings that seem to support Darwinism and free will over
creationism and determinism.
No evidence of 30,000 genes evolving over the course of
tens of millions of years can tell the whole story. Science can
claim to connect the dots of biology, not sketch the soul.
Philosopher: “If there were an omnipotent, omniscient
and perfectly benevolent god, then I think his or her
purposes are actually incomprehensible,” says Columbia
University professor Philip Kitcher. “The idea that 30,000
genes can explain or not explain anything is kind of absurd.”
Theologian: “Genes cannot explain the entire human
phenomenon,” says William May of Washington’s John Paul
II Institute. “Is thinking a function of genes? I think not.”
Biologist: “I don’t need to provide for you how many
ounces a soul weighs or how many base pairs it is coded by
in the DNA . . . to know that hope is worthwhile and hope is
real,” says scientist Robert Pollack, director of Columbia’s
Center for the Study of Science and Religion. “It is the reality
of hope that matters, not the physicality of the soul.”
Author: “It is not possible to step on God’s toes,” says
Neale Donald Walsch, whose four Conversations With God
books have been best sellers. “I think God chuckles at our
astonishment at these rather primitive revelations, very
much as we smile at a child’s first mastery of
multiplication tables.”
Proof of whether mankind was slow in the making or was
created in an instant is not likely to dissuade belief one way
or the other. Either version can be supported by the Old
Testament, embraced as sacred text by Christianity, Judaism
and Islam. And there are perhaps as many interpretations of
religious doctrine as there are mutations of a cell. Both are
uncountable. Similarly, there will be any number of ways
believers and non-believers will read the discoveries of the
human genome.
“The more we learn and the more we know,” Pollack says,
“the more we are aware of the boundaries set upon us by
the two facts of our lives: our free will on the one hand, our
mortality on the other.”
Two themes constant in religion and science.
Behind the Story: A Reporter’s Notebook
Ever since the world discovered Gregor Mendel's research into plant hybridization (first published in
1865 but apparently overlooked until 1900) scientists have been fascinated with the biological mechanisms that underlie inheritance. But the world would have to wait until February 12, 2001 for scientists
at Celera Genomics and the Human Genome project to decode the human genome and begin their
exploration of how humans function on a genetic level. Needless to say, anticipation of theit findings was
intense. For two weeks before the announcement, I privately interviewed the leaders of that research
effort, gathering the information I would need to explain their incredibly complex research to our readers. I felt priviledged to be granted advance access -- and broke out in goose bumps when Frances
Collins, of the Human Genome Research Project, showed me the first complete map of the human genetSteve Sternberg,
ic inheritance. I faced two challenges in describing this work: finding analogies that would allow me to
Medical reporter, Life
explain in simple terms one of the most complex systems in biology and predicting where this work
would lead. The overwhelmingly positive response from readers suggested the effort wasn't wasted.
Steve Sternberg has covered science and medicine for two decades for The Miami Herald, The Atlanta-Journal Constitution
and now for USA TODAY. He has won many national awards, including a prestigious John S. Knight Fellowship for
Professional Journalists at Stanford University, where he studied genetics in the laboratory of David Botstein. Last year, he
was awarded a master's degree in Science Writing from the Writing Seminar's program at Johns Hopkins University.
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Future Implications:
About Professor Smith
Professor Jan Smith has taught at the University level for over 20 years. She began her career as . . .
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