Beam of light quickly kills viral bugs, including the AIDS virus.

A ray of light for blood supply

USA Today

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."

-- Anonymous, June 13, 2001