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SCIENCE-FOR-THE-PEOPLE  March 2003

SCIENCE-FOR-THE-PEOPLE March 2003

Subject:

Re: Systems biology and genetics

From:

Maurice Bazin <[log in to unmask]>

Reply-To:

Science for the People Discussion List <[log in to unmask]>

Date:

Thu, 6 Mar 2003 10:08:14 -0200

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (260 lines)

Dear friends,
I want to thank Phil for putting very interesting material on our List (It
is reproduced below). It keeps me on my toes.
The 'Biologists' New Approach' is a wonderful case in point. I, a
physicist, learned about the shotgun approach to gene splicing and
insertion from interviewing John Fagan, an ex "gene jockey" (his words), as
he came to Brazil to help fight Monsanto's push for roundup et al. It was
amazing to learn about the shooting of gold and titanium pellets coated
with pieces of DNA into the cells of leaves of soybeans from someone who
did it. He then created a company that does tests to Certify GM-free food
products.

So it appears that the world of profit making has learned that "Systems
Biology" is their next step. Our critique then is still that "they" only do
it because it can bring further profits to the capitalist structures. It is
the criterion for choosing research topics and avenues that matters. In
this Dick's Cuba piece about its "biological weapons" for health comes
right in time.  Is this all there is to it?
Reductionism was perfectly adapted to capitalism's maximum egoism
structure, to its individualistic and competitive ideology. But now all of
this can go on at the "Systems Research" level, competition between labs
and their star directors. Is this all there is to it?
We must focus the struggle right and just keep asking: research and health
"care", and everything else (education for instance) in whose interest? and
show the answers, and show alternatives, and...Is this all there is to do?
And then we face South Africa's Premier and his position on AIDS. That's
when "subjective conditions" come in?

Keep on your toes!
Maurice



>Peculiar source for two interesting articles. --PG
>
>-----
>Biologists' New Approach: Do Not Shoot the Radio
>By Sharon Begley
>Wall Street Journal
>February 21, 2003
>
>How would a team of biologists fix a radio? First, they'd secure a
>large grant to purchase hundreds of identical working radios. After
>describing and classifying scores of components (metal squares, shiny
>circles with three legs, etc.), they'd shoot the radios with .22s.
>
>Examining the corpses, the biologists would pick out those that no
>longer work. They'd find one radio in which a .22 knocked out a wire
>and triumphantly declare they had discovered the Key Component (KC)
>whose presence is required for normal operation.
>
>But a rival lab would discover a radio in which the .22 left the Key
>Component intact but demolished a completely different Crucial Part
>(CP), silencing the radio. Moreover, the rivals would demonstrate
>that the KC isn't so "key" after all; radios can work fine without it.
>
>Finally, a brilliant post-doc would discover a switch whose position
>determines whether KC or CP is required for normal operation. But the
>biologists still can't fix the blasted radios.
>
>For those of you who haven't looked inside a radio lately, the Key
>Component is the wire connecting the external (FM) antenna to the
>innards of the radio, the Crucial Part is the internal (AM) antenna
>and the switch is the AM/FM switch.
>
>Biologists can't repair radios because their part-by-part approach
>fails to describe the radio as a system -- what's connected to what
>and how one part affects another.
>
>Biologists' affinity for the one-part-at-a-time approach, argues
>biologist Yuri Lazebnik of Cold Spring Harbor Laboratory on New
>York's Long Island, who dreamed up the radio analogy, is "a flaw of
>biological research today."
>
>For that, thank the events of 50 years ago.
>
>On Feb. 28, 1953, a Saturday, James Watson spent the morning at his
>Cambridge, England, lab piecing together cardboard representations of
>the "base pairs" in the DNA molecule. With that, he and Francis Crick
>realized that the master molecule of heredity is shaped like a spiral
>staircase, or double helix.
>
>This discovery ushered in the era of the gene and gave birth to a new
>field: molecular biology. The study of living things became a science
>in which progress meant describing the smallest bits possible,
>usually one at a time -- one stretch of DNA, one RNA, one protein.
>The double helix, Harvard University naturalist E.O. Wilson once
>said, "injected into all of biology a new faith in reductionism" -- a
>"shoot the radio" approach.
>
>As the world celebrates the golden anniversary of the discovery of
>the double helix with symposia, galas and media paeans, let me be
>contrarian: The reductionist paradigm launched by the double helix is
>just so 20th century.
>
>Don't misunderstand. Molecular biology was a rousing success. It
>reached its pinnacle with the sequencing of the human genome, whose
>final draft will be unveiled in April. But all good things must end,
>and there are signs that biological reductionism is one of them. It's
>pretty clear that making a parts list for an organism, even if you
>annotate it with those parts' functions, is no more adequate to
>understanding the complexity of a living thing than is listing the
>parts of a Boeing 777. Instead, you have to ask how the parts fit
>together and work together.
>
>The new approach is called systems biology, and it represents a huge
>departure from the reductionist paradigm. "Biology undergoes these
>revolutionary waves from time to time, after which nothing is ever
>the same," says biologist Eric Davidson of the California Institute
>of Technology, Pasadena. "This is one of those times."
>
>Catching the wave, the Massachusetts Institute of Technology last
>year launched a systems-biology program melding computer science,
>engineering and biology. In November, Eli Lilly & Co. established a
>systems biology lab in Singapore, where it expects to spend $140
>million over five years, and several biotech start-ups are hitching
>their stars to the new paradigm.
>
>Systems biology analyzes a living thing as a whole, not one gene or
>one protein at a time. "You have to look at all the elements in a
>living system to understand how they function," says biologist Leroy
>Hood. His seminal work on DNA-sequencing technology fell four-square
>in the reductionist camp, but in co-founding the Institute for
>Systems Biology in Seattle in 2000 he became one of the first and
>most prominent defectors.
>
>Not surprisingly, the systems approach represents an unsettling shift
>that "is not exactly welcomed" by many biologists, says Mr. Lazebnik.
>
>Partly, that's because "doing systems biology requires a huge change
>in the research culture," says Prof. Davidson. "In traditional
>molecular biology, each scientist works on his own gene, but the
>systems approach requires determining the effect of every gene on
>every other. You have to give up this 'my gene, your gene' stuff."
>
>But the payoff could be tremendous. At MIT, quantitative models
>showing the interconnections among cellular components -- much like
>the wiring diagram for a computer chip -- promise to predict
>unexpected properties of anticancer drugs such as Herceptin, says
>MIT's Peter Sorger. With any luck, the models will predict how to
>tailor cancer treatment to individual patients.
>
>-----
>DNA's Double Helix Isn't So Golden Now
>By Sharon Begley
>Wall Street Journal
>February 28, 2003
>
>If only more geneticists were Sherlock Holmes fans. They might find
>in the triumphs of the caped detective a much-needed epiphany.
>
>As Holmes realized in "The Adventure of Silver Blaze," it was the
>failure of a watchdog to bark on the night of the murder that
>provided a solution to the mystery. Geneticists face a similar
>puzzle. Sure, they can study people who both carry a disease gene and
>have the disease (breast cancer, melanoma, depression ...). But it
>might be a lot more illuminating to look at people who carry the gene
>but never get the disease -- a gene that doesn't bark. For these
>folks might show the way to prevention and cure.
>
>Last week, I wrote about a nascent revolution in which "systems
>biology" is overthrowing the reductionist, molecular-biology paradigm
>that has reigned for half a century, ever since James Watson and
>Francis Crick discovered that the DNA molecule is a double helix, 50
>years ago Friday. In particular, the new approach promises to explain
>why even the most publicized disease genes fall short of their
>billing.
>
>Of women who carry mutations in BRCA1 and 2, widely known as
>breast-cancer and ovarian-cancer genes, for example, 56% to 87% get
>breast cancer and 28% to 44% get ovarian cancer. Mutations in a gene
>called p16 lead to melanoma in 76% of those who carry it. The
>likelihood that a gene will lead to a trait or disease is called its
>penetrance. Anytime penetrance is less than 100%, something
>interesting is afoot.
>
>I could go on, but the point is that although geneticists and their
>media enablers give people the impression that DNA is destiny, it
>isn't so. Systems biology, which abjures the one-gene-at-a-time
>paradigm to incorporate all the genes and proteins in a cell, may
>explain why.
>
>Take penetrance. Biologists ascribe functions to genes based on
>studies of "inbred organisms with identical genotypes," says Lee
>Hartwell, who shared the 2001 Nobel Prize in medicine for discoveries
>in yeast genetics and is now president of the Fred Hutchinson Cancer
>Research Center in Seattle. "The problem is, things are very
>different in natural populations."
>
>Sure, you can say Gene X causes diabetes in an extended family, but
>what you are really saying is that Gene X causes diabetes when it
>interacts with precisely the genes those people share. Put the gene
>into 100 people with different genetic backgrounds, and maybe only a
>few dozen will get the disease.
>
>"This notion the public has been given that we'll genotype a person
>at birth and tell them their attributes is hogwash," says Dr.
>Hartwell. "A mutation against one genetic background will produce no
>effects, while a mutation against a different genetic background will
>produce a disease."
>
>To figure out how genes interact, biotech start-up Gene Network
>Sciences of Ithaca, N.Y., has produced what it calls the most
>detailed model ever of a human cancer cell. Incorporating more than
>500 genes and proteins, "it connects processes that have
>traditionally been studied in isolation," says Colin Hill, GNS's
>chairman. "In reality these genes and processes are connected, and
>you can't understand the behavior of the cell without knowing this
>biological circuitry."
>
>The model shows that "drugs hit more than one target," says Mr. Hill.
>"That's why you have side effects. We can also show that even when
>you knock out one gene or protein another can take its place, with
>the result that the cell doesn't die." That may explain why
>controversial cancer drugs like Erbitux and Iressa help few patients.
>
>That kind of knowledge could provide a desperately needed boost to
>drug discovery, which for too long has focused on single targets. As
>economists say, it's impossible to change only one thing; zap the
>target that you think causes disease and some other gene or protein
>might assume its function. Your patient is still sick.
>
>In contrast, a systems-level approach can identify feedbacks that
>neutralize drugs or cause side effects, says biologist Hiroaki Kitano
>of the government-funded Kitano Symbiotic Systems Program in Tokyo.
>As a result, a plethora of systems-biology companies are also
>drug-discovery companies.
>
>Systems biology isn't only about things going wrong. One of its
>singular accomplishments shows how things go right. Researchers led
>by Eric Davidson of the California Institute of Technology in
>Pasadena have produced a "gene regulatory network" that explains the
>embryological development of the sea urchin. Incorporating 55 genes
>so far, it shows that if enough molecules flow through the circuit,
>they bind to DNA and turn on genes.
>
>With this diagram, you can predict how any tweak will change the sea
>urchin. Prof. Davidson's group figured out, for instance, how to make
>a sea urchin develop two guts -- not exactly a holy grail of biology,
>but a proof of principle: It is a network of genes, not a single
>"gut" gene, that matters. A comparable wiring diagram for human
>development might show how to tweak stem cells so they differentiate
>into any of the hundreds of types of cells in the body.
>
>Systems biology is still in its infancy. But its early successes
>suggest traditional molecular biology, launched by the discovery of
>the structure of DNA, has run its course.
>
>Happy 50th Birthday anyway, double helix.


Maurice Bazin
Rua Pau de Canela 1101
Campeche/Florianópolis
88063-505    BRASIL
Fone: 55  48  237 3140
Fax: 55  48  338 2686 (Talvez você precise avisar.  May need oral warning)

e-mail:   [log in to unmask]

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