Rabbit gene works in monkey cells For the first time, a gene from one mammalian species has been made to function in cells from another mam­malian species using recombinant DNA techniques, Dr. Paul Berg of Stanford University has revealed.

Specifically, Berg and his asso­ciates, Dr. Richard Mulligan and Dr. Ruth Howard, have placed a segment of DNA that codes for the beta chain of rabbit hemoglobin into cells from an African green monkey.

To transport the rabbit gene to the monkey cells, they used the simian virus, SV40. To ensure that the gene would function once in the cell, they inserted it into SV40 DNA in such a way that the virus would provide the genetic fuse for the monkey cells to synthesize rabbit protein.

The Stanford technique appears to be a significant new tool for the ge­netic manipulation of eucaryotic cells. Much of the recombinant DNA work done to date has involved far simpler procaryotic cells.

News of this research inadvertently surfaced last week as Berg responded to questions by reporters at a meeting of the American College of Surgeons in San Francisco. He later said that he had not meant his remarks for pub­lication, since his work had not been submitted to a scientific journal. But when the story appeared the next morning in local newspapers, Berg issued a statement only confirming what had already been made public.

In discussing these reports with other scientists familiar with Berg's work, however, C&EN has been able to fill in some of the missing details.

The rabbit gene used by Berg and his colleagues was actually an artifi­cial molecule, created by a technique developed four years ago at California Institute of Technology. A molecule of messenger RNA for rabbit beta hemoglobin is used as a template to reconstruct the equivalent DNA molecule—the rabbit beta hemoglo­bin gene.

This process is necessary because in natural DNA the genetic informa­tion is actually scattered along the molecule. Sections that code for parts of a given protein are separated by spacer sections, which are not tran­scribed in protein synthesis and which serve no known purpose. In the artificial DNA molecule, those spac­ers are eliminated.

The key to the success of the Stanford technique, however, was knowledge of the complete DNA se­quence of the SV40. This sequence has only recently been determined by Dr. Walter Fiers of the University of

8 C&EN Oct. 30, 1978

Berg: confirms results

Ghent, Belgium, and Dr. Herman Weissman of Yale.

Knowing the sequence, the Stan­ford workers could choose enzymes that would excise a segment of viral DNA that makes a part of the virus' protein coat. Removing the structural protein caused a minimal disruption of SV40's functioning.

The excised sequence was then re­placed with the rabbit beta hemo­globin gene. Directly in front of this gene, within the viral DNA, was a se­quence of a type whose exact function is still not known, but which appears necessary if the gene behind it is to be recognized by the monkey cell as a template for making protein.

The final stage came when altered SV40 viruses were allowed to infect the monkey cells. As the viruses re­produced they commandeered the cells' protein-manufacturing ma­chinery to make virus proteins— except that one of these proteins, in­stead of being a piece of virus coat, was rabbit beta hemoglobin. D

FDA approves first antiviral drug Vidarabine, an injectable drug to treat herpes simplex encephalitis, has been approved by the Food & Drug Administration for marketing by Warner-Lambert Co. The disease, a virus inflammation of the brain, strikes more than 1000 Americans annually and is fatal to 70 to 80% of them.

"Vidarabine is the first drug ever approved by FDA for treatment of a life-threatening viral infection," says

FDA commissioner Donald Kennedy. "The data demonstrate that the drug can reduce [the rate of] fatalities from herpes simplex encephalitis from 70% to 28%."

Although most survivors suffered neurological impairments in the past, a National Institute of Allergy & In­fectious Diseases study found that only 50% have neurologic deficits after therapy with vidarabine, chemically 9-j8-D-arabinofuranosyl-adenine.

Incidence of the disease in the U.S., officially estimated at 1000 cases per year, actually may be 5000, an FDA spokesman says. Warner-Lambert predicts worldwide sales volume of the drug will be $15 million to $18 million in several years. A vidarabine ointment for herpes keratitis, an in­fection of the cornes, was approved in 1976. The firm is studying use of the drug against shingles, a painful nerve and skin infection by varicella-zoster (chickenpox) herpesvirus.

"It is a true antiviral, with so much promise for potential good in so many viral diseases, and it has opened the door to many avenues of research that were passed over because it was thought that development of antiviral drugs was an impossibility due to the nature of the viruses themselves," according to Dr. Robert A. Buchanan, director of clinical research for War-ner-Lambert/Parke-Davis pharma­ceutical research division.

Herpes simplex is an encapsulated DNA virus 180 millimicrons in di­ameter. Though the encephalitis may be suspected after detecting herpes simplex antibodies in blood, diagnosis must be confirmed by virus isolation from brain tissue.

Difficulties in estimating disease incidence arise because brain biopsies are performed only in very ill pa­tients. Also, the virus lives only four hours after a patient's death, so au­topsies may miss it.

Current treatment includes draining cerebrospinal fluid and ad­ministration of steroids to reduce intracranial pressure. There have been reports of successful therapy with intravenous 5-iodo-2-deoxyuri-dine and cytosine arabinoside. Pa­tients surviving an acute case may need physical and speech therapy. Some must be institutionalized for dementiaoruncontrolledinvoluntary movements.

FDA's Kennedy points out the relatively rapid six-month course of approval for injectable vidarabine. "FDA reviewed the scientific data on vidarabine as quickly as possible after it was submitted," he says. "This is an example of the preferential treatment we give to new drugs that represent major advances in therapy." •