Of pharmers and chimeras

The green fields that ostentatiously carpet the hills of Scotland are home to the drug factories of the Roslin Institute. These factories produce only a modest amount of gas, and nobody in the neighbourhood is complaining. After all, these ‘factories’ are sheep, genetically engineered to produce human proteins in their milk.

Welcome to the new world of pharming, a wonderfully low-impact technology that holds great promise for victims of emphysema, cystic fibrosis, thrombosis, haemophilia, AIDS, arthritis, malaria and more.

The pharmer of the future might expect a herd of 100 or so sheep to satisfy the entire world market for certain complex drugs that are difficult to manufacture any other way. Each animal, over its lifetime, could be worth millions of dollars. Because these sheep have been engineered to have human genes, they are called transgenic animals or chimeras, in honour of the mythological Greek creature combining a lion, a goat and a serpent. In the myth, it was Bellerophon, straddling the winged horse Pegasus, who finally slew the fire-breathing chimera.

Jeremy Rifkin is a modern-day Bellerophon, fighting to stop pharming – and any other research involving chimeras, for that matter. Since millions of lives are at stake, he had better have a good argument. Rifkin, president of the Washington-based Foundation on Economic Trends in the USA, is a veteran gadfly, and is skilled at getting press coverage and congressional hearings. So, for better or worse, his thoughts count.

Rifkin is worried that scientists will go insane and start to create hideous crossbred creatures that would make the Island of Dr Moreau look like Green Acres. This would be a nightmarish use of the technology, and scientists have universally agreed not to pursue it. Working hand-in-hand with their bioethics committees, these scientists have devised protocols to prevent just such atrocities.

Rifkin isn’t soothed by the assurances of the scientists, and has long attempted to influence the government to pass more restrictive laws – laws that would ban vast stretches of medical progress.

Recently, Rifkin teamed up with Stuart Newman, a biologist from New York Medical College who shares Rifkin’s fears. With Newman as his Pegasus, Rifkin hatched a clever plan. He asked Newman to think up the most disgusting chimera he could imagine, and then try to patent it. He came up with two, the human-chimpanzee and the human-mouse. Both have a hefty cringe factor.

If they could get a patent, they reasoned, they would be in a position to deny any other applicants, thus sparing the world from a horrible mutation. And if they couldn’t get a patent, they could sue the US patent office and force a showdown over gene patents in general. In either case, they would garner a lot of publicity and encourage people to become disgusted with transgenic research and anything that might mix the genes of humans and animals.

For over two decades, the patent office has issued patents on living creatures that were created, for the most part, by splicing genes. But they draw a line when the product of the patent is a human or a human embryo. That makes sense; but to Rifkin and Newman, these patents start us down that dreaded slippery slope to human debasement. In their opinion, the only way to avoid this fate is to ban gene patents altogether.

But what the heck are these guys talking about? There are already many amazingly useful chimeras – each one devised for a specific therapy. Here’s a look at the actual science that has Rifkin and Newman so alarmed.

The pharmer’s way to make a chimera is to insert a specific human gene into an animal, like the Roslin sheep, so that a human protein will be secreted in its milk. Mammaries are favoured because they are highly productive secretory organs, but scientists have toyed with kidneys and salivary glands as well.

Transgenic lab mice that carry various human genes have been patented for years. But they are obviously mice, not the humouse monsters envisioned by Rifkin and Newman. These mice are used most often for testing. Biologists have always known that testing a mouse for human drugs only gives a loose approximation. Using human genes makes the tests far more accurate, minimising the need for large-scale human testing.

A very small chimera is formed when human genes are spliced into bacteria or yeast. This is how the biotech companies are brewing most of their miracle drugs, like human insulin, in fermentation tanks. The products of these patented bacteria have already saved hundreds of thousands of lives.

Coming soon: human genes transplanted into food crops, so medicine can be grown in the field – a new branch of pharming. The fruits of this research could simply be eaten or used as inexpensive diagnostics, bringing sophisticated testing to a wider market.

Another way to create a human-animal chimera is to transplant, say, a pig valve into a human heart. These people still expect to be treated like people. They don’t exhibit porcine behaviour. Rifkin should have a heart-to-heart talk with these chimeras before he condemns their heretical gene-mixing.

Natural chimeras happen more often than one might think. Fraternal twins that share a placenta often have two different blood types, one from each twin, due to the mixing of their fetal stem-cells in the placenta.

Incredibly, the most common chimera may be your mother. Scientists have recently discovered that some – and perhaps all – mothers have DNA from their own children circulating in their blood for decades after childbirth. In a sense, the mother inherits DNA from her children. This is clearly weird, but totally natural. And it’s often troublesome -researchers speculate that when the mother’s immune system tries to eliminate the foreign DNA, it can lead to autoimmune diseases like lupus and arthritis.

Rifkin needs to be reminded that just because it’s natural, doesn’t mean it’s good. In fact, the opposite is more often the case, which is the whole point of science: to transcend our natural limitations.

A newly discovered chimerism in transplant patients has researchers buzzing: after a transplant, cells from the host start to infuse into the donated organ. Scientists have discovered that up to 20 percent of a donor heart may be composed of host tissue within days of the transplant. This implies that an organ does not need homogeneous DNA to work properly, and that genetically different cells can work together remarkably well.

Researchers have also discovered that bone marrow transplant patients soon have donor cells throughout their bodies. Since marrow contains stem-cell precursors to the blood and immune system, you can see how they might get around. After a while, they infiltrate muscle, liver, brain, kidneys and probably other organs as well (1).

Bone marrow and other transplants would thus be banned by Rifkin’s anti-chimera crusade. Here Rifkin is echoing the howls that attended the first human transplants. Those critics insisted that transplants would demean life and destroy our souls. They demanded that research be halted immediately, before lasting damage was done to the human race. The hue and cry died down when, as predicted by the scientists, transplants enabled people to extend their useful lives without sacrificing their souls.

Another so-called chimerism involves using an animal egg to create human stem-cells. Here, the biological magic is that egg cells, pretty much regardless of species, are very accommodating. They can take an astonishing variety of donated DNA and ‘remodel’ it so it can be duplicated. The procedure involves snipping a bit of skin from the patient to get the DNA. After removing the nucleus from the egg, the patient’s DNA is inserted. Given a tiny shock, the egg proceeds to remodel the DNA, and then it begins to cleave. After a few divisions, clinicians can harvest the stem cells for therapeutic uses.

Recent announcements from the biotechnology company Advanced Cell Technology (ACT) in Boston, USA, indicate that a cow egg can remodel human DNA. If so, it could eliminate the need for human eggs to create human stem cells. This means that you could amplify your own cells, without involving another human being. It also means the procedure could become cheap and commonplace. When it does, scientists hope to cure heart disease, Alzheimer’s disease, Parkinson’s disease, diabetes, arthritis, AIDS, and nerve damage – all with variations on the single theme of stem-cell therapy.

Rifkin condemns this procedure as chimerism, but these cells don’t have any nuclear DNA from the animal egg – the egg’s nucleus is completely removed beforehand, or the procedure won’t work. These cells are, therefore, not chimeras at all. They are simply a thin scum of cells in a petri dish; therapeutic tissue that is genetically identical to the patient. So, although this procedure gives Rifkin the willies, it doesn’t produce chimeras. Again, nobody is attempting to clone herds of humans this way, only therapeutic cells.

But the most amazing chimera of all is you. Deep in your DNA are remnants of your animal past – and more. You share 99 percent of your genes with monkeys (2). If you transplanted any of these genes, it wouldn’t change a thing. Over half of the genes in a fly have been found in humans (3). In fact, you share a lot of genes with plants and even bacteria. Stranger yet, your entire DNA is shot through with viral genes, inserted by retroviruses that infected several of your ancestor’s germ cells over the past three billion years. Your DNA – everyone’s DNA – represents an accretion of insults we’ve survived.

We can lump all these chimeras into two groups: animals with extra genes and humans with extra genes. In the first case, the whole point is to genetically engineer an animal that is eco-friendly and produces a useful protein. These are obviously animals and would never be mistaken for humans. In the second case, we are clearly talking about humans, with all their attendant rights. Those patients who have been saved from certain death by mixing genes are nonetheless human, and are not too concerned about Rifkin’s ideological problems with their therapy.

Thus far, it’s pretty obvious which are the animals and which are the humans. But Rifkin is worried about that slippery slide into Monsterville with those half-human half-monkey creatures. We all need to be on guard against mad scientists. But the fact is that no sane scientist wants to create a monster. Scientists are driven by the desire to learn and to help mankind. Of course they’re chasing grants as well, but who’s going to pay them to create a monster?

The slippery slope argument can be used against anything, but as the chains of causality get more tenuous, the results can become absurd. Rifkin seems unaware of how surreal he sounds. He says, ‘I have spent so much time focusing on how eugenicism is now becoming commercial and market-driven. If there is an enemy, it is all of us who, for good reasons, want healthy babies’ (4). So Rifkin’s slippery slope starts with healthy babies. Now there’s an interesting crusade.

Should we tinker with our genes? Why not, if we can cure a heinous disease? Why not eliminate deadly genes from the human gene pool, like the ones for Huntington’s chorea or Tay-Sachs? If you think these genes might come in handy, back them up on a computer tape – but surely nobody would wish these diseases upon any child. We wiped the DNA for smallpox off the face of the Earth, and we’re closing in on polio. Why not take on some of those rogue human genes?

That’s not to encourage complacency. Commanding our own destiny requires thoughtful oversight. That’s why leading scientists like Ian Wilmut, the man who cloned Dolly and whose work led to drug-producing sheep, always encourage public debate. Wilmut says, ‘What we want is to stimulate an informed public discussion of the way in which the techniques might be misused as well as used and to ensure legislation is put in place to prevent misuse. But we’re also concerned that we don’t throw the baby out with the bathwater. There are real potential benefits, and it’s important that the concern to prevent misuse doesn’t also prevent the really useful benefits that can be gained from this research (5).

Then there is the question of gene-tinkering, stuff that doesn’t cure or cause harm, but is designed to ‘improve’ a child. That could be anything from blue eyes to higher intelligence. This is an area where Rifkin and others get quite concerned – a place they feel highlights the evil potential of eugenics. But how problematic is this?

One of the worrisome things about playing with the germ line – as opposed to the DNA of a single individual – is that it seems so irreversible. The concern is that a gene, once released, might somehow get out of control and bring down all of civilisation. But once we understand how to change a gene, we will also know how to change it back. Genetic engineering is not a one-way street.

That doesn’t mean there are no problems, but Rifkin’s monsters will never come to pass – partly because they are already illegal but mostly because there is absolutely no need for them. Rather than trying to ban useful treatments because of far-out hypotheticals, we should just try to deal with the current crop of questions. In the meantime, we shouldn’t deny therapy to sick people simply because a madman might someday misuse the technology.

Rifkin wants to stop more than just chimeras. He also wants to end the practice of patenting genes. Actually, patents aren’t issued for the actual genes, but for therapies and diagnostics that make use of the genes. The specific genetic code is specified in the patent, but only as a way of defining the limits of ownership. Without patents, the entire multi-billion dollar biotech industry would collapse overnight, stranding millions of patients in the process (6).

The American patent system isn’t perfect and patents have sometimes been abused by the pharmaceutical industry, but it has given rise to the most astonishing growth of therapeutic medicine in the world. The best proof of its success is that countries without an effective patent system have not created comparable drugs. Indeed, they are often reduced to stealing them from the countries that do.

Stuart Newman says, ‘Private ownership of inventions is not the only way progress has been made in the history of science and medicine’. That’s true, but it is demonstrably the most efficient way. Newman told the LA Times that: ‘there really is no boundary on what you can do with human life. There’s no natural stopping point. I think it will ultimately lead to genetically engineered human beings made for sale.’ This sounds pretty apocalyptic, but what is the good doctor talking about? There are plenty of boundaries on what you can and can’t do to human beings, and selling them is not one of the options. The thirteenth amendment to the American constitution banning slavery pretty much covers the bases.

Whenever the lines start to blur, whenever people are affected without their consent, we need to exercise diligence. But rather than fretting over slippery slopes and theoretical monstrosities, we should take each case as it comes, evaluating the pros and cons, and making thoughtful decisions.

Rifkin needs to chill out and realise that science, for all its warts, has increased the healthy lifespan of Americans and others in the developed world two-fold in less than a century. Oddly enough, for a group of people who are often equated with Dr Frankenstein, scientists are largely motivated to make life better. And, in a capitalistic country, it’s hard to make a living by creating things that people don’t want.

That’s not to say scientists won’t make mistakes; they will. It’s unavoidable when charting new territory. But bioethics is not an afterthought in this kind of research, and scientists are eager to have independent guidelines. The best way for Rifkin to shepherd this research safely would actually be through seeking further federal funding, not a ban. With funding comes a complete set of guidelines and a responsibility to share the results of the research. With that kind of public oversight, it is easy to maintain a monster vigil.

By denying federal funds for the past decade, the government has effectively privatised stem-cell research. As a consequence, very little of what the researchers know is in the public record. If the science is banned, the work will simply go abroad, where it will enjoy even less scrutiny.

Given all this, it’s hard to see the point of Rifkin and Newman’s stunt. It may work to scare the public, but the only ones proposing to make monsters are Rifkin and Newman. Real scientists make their living by helping people. Banning gene patents and chimeras won’t save a single human life. On the contrary, it threatens the health of millions. To deny these people their therapy would require a very good argument indeed. Rifkin just doesn’t have it.

Scott Anderson is a science writer in Northern California. He is writing a book on stem cells with Dr Ann Kiessling-Cooper, a pioneer in the field.

Read on:

spiked-issue: Genetics

(1) See more on how bone marrow transplants can infiltrate muscle, liver, brain and kidneys

(2) Human and chimpanzee functional DNA shows that they are more similar to each other than either is to other apes (.pdf), a paper by Wilman et al

(3) Complete mouse DNA map soon, BBC News 2 June, 2000

(4) Jeremy Rifkin:
fears of a brave new world, UNESCO Courier

(5) Dr Frankenstein, I presume?, Salon.com, 24 February 1997

(6) US human/chimpanzee life form patent challenge by Jeremy Rifkin & Stuart Newman will now go to the federal courts, reproduced from the Washington Post on the Organic Consumers Association website

© 2002 Scott Anderson