A ray of light for blood supply
Revolutionary process kills HIV, other
diseases
By Robert Davis
USA TODAY
A venture that began in a scientist's garage in Berkeley,
Calif., appears to be on the verge of revolutionizing blood
donations by using a beam of light to quickly kill viral bugs,
including the AIDS virus.
The process, known as Helinx, uses ultraviolet light to
fire a genetic "bullet" that kills any virus, bacterium or
parasite by attacking the DNA or RNA, the strands of genetic
code at the heart of the cell.
Successful tests in hundreds of patients across the nation
are raising hopes that the nation's blood supply could soon be
rid of the killer viruses and, perhaps more important, bugs
linked to similar but yet unknown diseases.
For Third World nations where AIDS is more common and blood
testing more primitive, the technology promises a quick and
inexpensive method for stopping the spread of the lethal
disease. The process rids donated blood of everything that is
DNA-driven, from malaria to hepatitis.
In the USA, the technology could increase the size of the
blood pool. Donated blood that today is discarded because
imperfect tests tag it as questionable could be used to save
more lives. And all of the donated blood would be considered
safe after treatment.
The process is promising partly because it's simple.
"When we are treating a bag of blood, we throw the switch
and we kill all of the bugs," says Stephen Isaacs, CEO of
Cerus of Concord, Calif., which developed the technique. "When
we turn off the light, everything stops."
Studies have shown that the process rids donated platelets
of bugs and does not harm the product or the recipient. But
the Food and Drug Administration is not expected to approve
the process until next year, after studies of 600 patients are
submitted for the agency's review.
The technology is among several that the blood industry is
trying to develop to make transfusion medicine safer. Others
include better testing to detect diseases; solvents that are
already on the market that "scrub" away HIV and viruses such
as Hepatitis C; and blood substitutes that reduce the need to
use human blood products.
The Helinx technique is distinctive because it attacks the
virus at its root -- the DNA and the RNA. When these strands
separate, they allow the cell to reproduce. The Helinx process
binds these strands so they can't divide.
"It's a rifle shot," Isaacs says. "You eliminate the bad
guys and all of the cells that you want for transfusion retain
their function."
There is an urgent need for safer blood.
More than 10,000 people have developed AIDS because they
contracted HIV from a blood transfusion or they got the virus
from somebody who had a tainted transfusion. Most of those
infections occurred before modern safety measures were in
place, but a handful of such cases are still reported each
year.
Each pint of donated blood is split into several components
and then used to treat different medical needs. Red cells
carry oxygen, for instance, and plasma helps control bleeding
through clotting.
The Helinx process can be used to clean all of the blood
components, but it has been used most widely in platelets,
cell fragments that help form clots to stop bleeding and are
used to treat leukemia and other cancers.
Here's how it works: Inside the bags that are used to
collect the blood products, there is a solution called a
psoralen compound. When the donated blood mixes with the
solution, the molecules from the compound mingle with the DNA
and RNA of any virus, bacterium or parasite. When exposed to
an ultraviolet light, the psoralen compound links with the DNA
and creates a permanent bond. When the light is turned off,
the chemical reaction ends but the bonds remain. The chains
with the codes for life then cannot "unzip" to reproduce, so
the disease cannot spread.
HIV rendered harmless
The result is that the virus remains in the blood and is
transfused into the recipient, but does no harm. If a virus
can't replicate, it can't hurt its host. The Helinx technology
deactivates the virus.
Before the technique can be applied widely in the USA, the
FDA must determine whether the process is safe and effective.
The FDA can't discuss specific technologies under review, but
the impact on the patients is the agency's key safety focus.
We're concerned that other proteins and cells that are
necessary for the efficacy of the product aren't altered in
such a way that they could produce immune reactions or an
allergic reaction," says Mark Weinstein, director of the
hematology division at the FDA.
The FDA is reviewing studies of how the blood products
treated with the Helinx technology compared with conventional
blood products in terms of carrying oxygen, reducing bleeding
and other medical uses.
Some benefits already are clear. One of the methods on the
market today to rid plasma of the virus that causes AIDS is a
solvent that scrubs the HIV away. To perform this technique,
large quantities of plasma -- as many as 2,500 individual
donations -- are mixed in one vat. The HIV is then "scrubbed"
away, but other diseases that might have gone from one donor
to one recipient are then mixed with donations from thousands
of others. The process eliminates a deadly disease but might
spread less threatening ones.
Weinstein says that though such pooling allows workers to
eliminate the big-gun viruses such as HIV, it increases the
risk of spreading lesser classes of viruses such as hepatitis
A, which are not removed by the solvent. "You have all of the
material pooled together so there can be a higher probability
for the other viruses to be spread," he says.
Paul Holland, who runs the Sacramento blood centers and has
worked as a safety monitor on the Cerus clinical trials, says
putting an end to the pooling process would be better for his
blood center.
"With the Cerus approach, you can apply it to any unit of
blood at your blood center, and you can do it in a few
minutes," says Holland, whose blood centers collect 165,000
units a year from 17 California counties. "That's a huge
advantage. I don't want to ship it off to New York or
Timbuktu, and then I get it back and it's all combined. I want
to keep control of it."
Unknown threats
While the new technology promises to stop these rare cases
in which known viruses are spread, even more exciting to some
is that the process would halt transmission of threats unknown
or unidentified.
One reason HIV spread so widely across the nation via the
blood supply in the early 1980s is that there was no way to
detect the disease in its earliest stages.
When a disease first emerges, it is impossible to screen
for it until doctors have some understanding of how the virus
works.
Even when the disease is better understood, the most
sensitive tests could miss some cases. Current screening tests
require the infection to be advanced enough to be detected.
When undetectable traces of the virus exist in the blood, they
can multiply later, both in the donor's body and in the
patient who gets the blood transfusion.
The result is that today, the chance of getting HIV from a
blood donation is still between 1 in 500,000 and 1 in 800,000
transfusions, the Centers for Disease Control and Prevention
estimates. The chance of getting hepatitis C (HCV) from a
blood donation is less than 1 in 1 million units transfused,
the CDC says. But with roughly 14 million transfusions a year,
people still get infected with these deadly diseases.
Even so, public health experts see the blood system as safe
as far as HCV and HIV are concerned.
"The blood supply is safer than it's ever been," says
Miriam Alter, chief of the epidemiology section at the CDC's
viral hepatitis division.
But experts know that the high level of safety could be
shattered tomorrow if a new virus like HIV or HCV were to
emerge.
"The real issue is being able to detect new or emerging
infections that we don't even know about yet," she says. "If
there is a process that can inactivate even unknown pathogens,
that would be a great advantage and an extra margin of
safety."
Alter and others have seen firsthand what happens when a
virus sweeps through the blood supply before doctors know it's
there.
HIV raged in the nation's blood supply for years as the
medical system struggled to understand the disease.
Since the AIDS epidemic began in 1981, the CDC says, 9,047
people have contracted AIDS from blood transfusions. Many of
those people infected by blood donations then went on to
infect others.
An additional 990 adults have been infected through
heterosexual sex with someone who was infected through a blood
transfusion, the CDC says. And 185 babies have been infected
by mothers who either got HIV from a blood transfusion or had
sex with someone who got HIV from a transfusion.
The CDC tracks only those who progress to AIDS. There are
countless more people who have been infected with HIV from a
blood transfusion but have not developed AIDS.
Most of the damage was done before 1985, when blood
agencies began using a test to check for HIV.
Public health officials hope for the day when a better
safety net would prevent such tragedies by killing any and all
bugs in blood.
"With a new pathogen, you don't know if this is a virus, or
whether it's a lipid- or non-lipid-virus," Weinstein says.
"These broad-based viral inactivation methods are one way of
addressing the problem."
For nearly 20 years, Larry Corash has wanted to find a way
to kill unknown viruses in donated blood.
In 1982, he was a blood doctor who could only watch in
horror as his transfusion treatments for his hemophiliac
patients infected many of them with HIV.
"The HIV epidemic was in pretty full blast," says Corash,
now chief medical officer of Cerus. "A lot of my patients were
getting HIV." Those patients were among the 5,357 hemophiliacs
who are known to have gotten AIDS from blood donations.
As the former National Institutes for Health blood
researcher began hunting for a way to rid the virus from the
blood supply, his search led him to Steve Isaacs, a biochemist
who had a knack for making molecules that can work like
genetic robots.
Isaacs was a researcher in what would become one of the
University of California-Berkeley's most famous laboratories.
John Hearst, then a chemistry professor at Berkeley, headed
the lab that focused on using light to ignite chemical
compounds.
Working with other scientists who would go on to win Nobel
Prizes for their work, Isaacs and Hearst, who is now with
Cerus, discovered that they could bind their manmade molecules
to DNA by simply striking it with a beam of ultraviolet light.
Their process sent ripples through labs around the world.
Others wanted to play. After Isaacs' work was published,
scientists contacted him and asked for some of the psoralen
compound so they could do other experiments.
A little garage business
"I had always had a little business gene in me, so I
thought, 'Why don't we start a little garage business?' "
Isaacs says. "I was spending a lot of time packing this stuff
up and sending it out for free to researchers around the
world."
When Isaacs met Corash, who was desperate to tie up and
damage the DNA within the AIDS virus in donated blood, a
strong business bond was formed.
Corash says there have been stressful times, "but we always
come back to the science. That is the bond that holds people
together."
Corash says the technology will have an impact beyond the
blood supply.
The company has high hopes for the method as a cancer
treatment. The technique is being tested in trials designed to
create a vaccine against the Epstein-Barr virus. By exposing
coronary artery tissue to the compound and then the light, the
arteries may stay open after an angioplasty. And the compound
is being used to modify immune cells for transplants.
When you can turn off DNA with the touch of a light switch,
Corash says, "the mountain is endless."
