Researchers Engineer Hens that Make Drugs in Eggs

Scientists at the Roslin Institute, which produced Dolly the cloned sheep, have genetically engineered chickens to produce drugs in their egg whites. Helen Sang, the lead scientist at the Roslin Institute in Midlothian, Scotland, talks about the findings.

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IRA FLATOW, host:

This is TALK OF THE NATION Science Friday. I'm Ira Flatow. As any pharmaceutical company will tell you, making drugs is a painstaking and very expensive undertaking, so researchers are always on the lookout for ways to speed up the process and make them cheaper.

For instance, they have tweaked cows to produce drugs in their milk so every time the cows give milk, they also give a fresh supply of drugs. But in a twist on this approach, scientists at the Roslin Institute - that's the institute that created Dolly, the cloned sheep - well scientists at Roslin have genetically engineered chickens now to produce drugs in their egg whites. Some of them - some of these drugs that are used to fight cancer.

With every batch of eggs comes a fresh supply of drugs. Unfortunately, getting the drugs isn't as easy as scrambling up an omelet. The researchers report on their research in the current issue of the journal Proceedings of the National Academy of Sciences, and the leader of the team joins us now to talk about their work and its potential to change the way drugs are made.

And if you'd like to discuss it with her, please give us a call. Our number: 1-800-989-8255, 1-800-989-TALK. As always, you can surf over to our Web site at sciencefriday.com.

Helen Sang is a principal investigator at the Roslin Institute in Midlothian, Scotland. She joins us today by phone from her home there. Good evening, and welcome to the program, Dr. Sang.

Dr. HELEN SANG (Principal Investigator, Roslin Institute): Good evening.

FLATOW: Is it that simple to make an egg with drugs in it?

Dr. SANG: It's not that simple. It's certainly taken us a long time to get to this point.

FLATOW: Tell us how you did it.

Dr. SANG: Well, what we've done is - the really hard part was trying to make genetically modified chickens at all in the first place. And what we've done is take advantage of a virus vector that's been designed - actually with human gene therapy. But we find that if we use this virus vector and inject it into chicken embryos in freshly laid chicken eggs, that they can take in foreign genes into the chicken chromosomes.

So we use this virus vector, and now we've put in our own foreign gene, and the foreign gene we use has the sequences that drive expression of one of the main egg-white proteins linked up to the sequence for, in our case, human beta interferon. And we used the virus vector to introduce that gene into a founder bird, and then we breed from that bird to get our genetically modified hens.

FLATOW: So you get a transgenic chicken first.

Dr. SANG: We get a transgenic chicken, yes.

FLATOW: And then you breed that, and out comes the eggs that the egg whites have the drug in it.

Dr. SANG: That's right. So the foreign protein, the therapeutic protein, is only expressed in the ova of hens when they're laying eggs but it becomes part of the egg white.

FLATOW: What kinds of drugs are you using? You mentioned interferon.

Dr. SANG: Yes. So interferon is an example of a cytokine, and these are used to treat diseases that are ranging from viral diseases through to some cancer treatments, and the second type of drug that we've shown can be made in chicken egg white is a form of antibody, and there are a lot of antibody drugs in development, and some of them already out in use - the best known of which is Herceptin, which is used for treating breast cancer.

FLATOW: Now the idea is not to feed the eggs to people, right? I mean…

Dr. SANG: No, that's right. The idea is that this is a way of making the protein drug. But after that, we will have to purify it out of the egg white, extract it from the egg white and make sure that there's no egg white proteins left. And once we have a pure drug, it will then have to go through clinical trials, as any new drug has to.

FLATOW: How efficient is this compared to the cow's-milk method for making drugs?

Dr. SANG: I think it's - in some ways, it's of comparable efficiency, but we hope that it will be a more flexible system because it takes a lot shorter time for hens to reach maturity and lay eggs, so it takes about five months, whereas cows take a couple of years until they are producing milk. And also, of course, birds are much easier to work with, and it's cheaper to maintain single birds than it is to start working with cows.

FLATOW: And drug companies are already used to working with chickens because they make the flu vaccine and things like that in the eggs, right?

Dr. SANG: That's quite right. They already produce birds, grow birds up in relatively sterile conditions so that they can grow flu vaccine in their eggs.

FLATOW: Now what kind of drugs would this not be suitable for? What do you have to have? You know, what method - what won't it work in?

Dr. SANG: Well, this is really suitable for the more-complicated protein drugs. So there are a lot of new drugs coming along that are derived from our own natural proteins, and interferon beta is one of those. And really we are looking to produce drugs that can't be produced in more-simple systems. So they're usually proteins that require sugars to be added to the protein after it's synthesized to make it fully functional.

FLATOW: Now what do you say to the person who says uh-oh, if we get into making - allowing chickens to have drugs in their eggs, these chickens are going to escape the hen house and get out into the environment, and people could eat these eggs and get drugs they shouldn't be getting.

Dr. SANG: I think probably if they ate the eggs with the drugs in there, the protein would be degraded by the digestive juices in the stomach and the colon. So it's very unlikely they would take the drug in anyway. But our chickens are certainly housed in conditions where they can't escape, and there aren't many wild chickens, certainly here in the U.K., for them to go out and breed with, so I think it's a very low risk.

(Soundbite of laughter)

FLATOW: (Unintelligible) Frankenchicken coming.

Dr. SANG: That's right. I think it's little risk for people.

FLATOW: 1-800-989-8255. Douglas in Boca Raton, Florida. Hi, Douglas.

DOUGLAS (Caller): Oh hi, Ira, you do a wonderful job. I'm calling from sunny Florida here, and I'm Scottish, and I just wanted to compliment your guest on her obvious capability and wonder whether there's anything particular going on in Scottish education that's pushing the Roslin Institute to the front in pharmaceutical research.

Dr. SANG: I think it's - we've always - and I think in the U.K., biological research in general, we're encouraged to think in terms of pharmaceutical or other commercial applications of our research, even though it's largely driven by blue skies, wanting to know things. But if we spot a potential application of our research, then we get a lot of support to take it further towards industry.

FLATOW: Thanks, Doug, for calling.

DOUGLAS: It's good to see Edinburgh doing so well. Thank you so very much.

Dr. SANG: Thank you.

FLATOW: Thanks for calling. 1-800-989-8255. Okay, so what is the next step, Dr. Sang, in going ahead with getting, you know, mass-produced, you know, drugs from eggs? How far down the road do we need to go? How many years away are we?

Dr. SANG: We're quite a long way away, I think, in terms of actually having a drug that is ready to go into patients, because anything that we produce will have to go through all the clinical trial process, which as everybody knows takes a considerable number of years. But it's important to do that to make sure that they're completely safe, and that they are efficacious, and without bad side effects.

But our next steps are to try and increase the amount of the protein drug in each egg, particularly if we want to make antibodies like Herceptin because each individual patient will need large doses of these proteins, and they'll need multiple doses.

FLATOW: What percentage are we at now in your research?

Dr. SANG: Pardon?

FLATOW: What percentage - how are you are at now? Where would you like to get to be?

Dr. SANG: We're only a few milligrams of protein per egg, and I think we'd like to get to hundreds of milligrams of protein per egg. But we don't want to be too greedy because I think if we try to express too much of the protein, we might upset the birds, and we might affect the formation of the egg.

FLATOW: Are you mostly looking at drugs for the mass market that might take the place of production in the normal way that it's done now, or you're looking for more orphan drugs or cancer drugs?

Dr. SANG: I think it's too soon to say, because we need to really develop the whole process a little bit further to see how cost effective it is, because of course if it is cheaper and you can, say, only have 50 hens producing a particular drug, then it might be a potential production system for the drugs where there's not such a big market. But we're not at that point we can make those sort of recommendations yet.

FLATOW: Is there an ultimate animal that might even be better than a chicken?

Dr. SANG: I think what there's going to be is horses for courses. I think that we're developing chickens for making proteins. The company (unintelligible) in Massachusetts, who are using goats - GTC Biotherapeutics - and they have a product produced in goats milk that has been licensed for patient use in Europe. So there will be goats. There's companies still working with cows, but there are the other methods that are already being used, that's making proteins in mammalian cells or in yeast or in bacteria. And really it will depend on each individual drug, which is the best system.

FLATOW: And there might not be one over the other. You might have a few of them.

Dr. SANG: Yes, I think there will always be several different systems depending on the real specific attributes of each drug.

FLATOW: Do you think you might be able to make a vaccine this way?

Dr. SANG: Yes, it's something people have talked about, actually, in terms of using eggs without extracting the proteins and expressing vaccines that would then be administered orally. That is by eating the egg.

FLATOW: It's possible, huh?

Dr. SANG: That is possible.

FLATOW: That's something you're looking into?

Dr. SANG: That's something we thought about a bit and hopefully we'll explore a little more.

FLATOW: Mm hmm. And so you immediately are going to try to find ways of making more drugs per egg?

Dr. SANG: That's right.

FLATOW: And how do you do that?

Dr. SANG: We use what I would call transgenic tricks, because there's not many transgenic or genetically modified chickens about, but there are a lot of genetically modified mice which have been studied for all sorts of reasons to do with medical research, because they're used as a model for disease in humans. And there are a lot of little tricks that are being learned in genetically modified mice for getting different levels of gene expression, and that's what we'll look to to try and get some ideas from those experiments.

FLATOW: So you might put the mice into the eggs?

Dr. SANG: No, no, no.

FLATOW: The mice genes?

Dr. SANG: We might just copy the tricks that people have used in mice to get higher levels of expression in our chicken eggs.

FLATOW: So really just talking about an engineering problem here.

Dr. SANG: It's a sort of - it's a molecular engineering problem.

FLATOW: Well, good luck to you, and thank you for staying up late and taking time to talk with us. Have a good weekend.

Dr. SANG: You're welcome. Thank you. Goodbye.

FLATOW: You're welcome. Helen Sang is a principal investigator at the Roslin Institute in Scotland, and she joins us today by phone from her home. We're going to take a short break and when we come back we're going to switch gears and talk about the weather. If you've been having weather - some real weather - and you've been living out in the Plains states, you've been getting socked in with those blizzards, you're out in California watching the frost of the ice on your citrus - well, you know, it's been a really wild winter.

Back here East we had our first bit of snow yesterday. We thought we were going to go through the whole winter without some, but winter has finally arrived, but it's going to be warm again today. So we'll talk about whether this has anything to do with global warming or is it a natural trend, or what do you think? Give us a call. Our number 1-800-989-8255. Stay with us. We'll be right back.

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