Journal of Scientific & Industri al Research Vol. 62, June 2003, pp 635-648

SCI-TECH UPDATE

Gene maps-building better animals for meat

Recent di scoveries about the genetic code of animals could be used to rai se cattle, pigs and shrimp more efficiently , resulting in s ignificant economic gains for the $240 billion worldwide meat industry .

"We are now at the cusp of some breakthroughs in animal sc ience that will offer enormous business opportuniti es," said Clifton Baile, the CEO of ProLinia, a genomics startup company, and a professor of animal science at the University of Georgia.

The developments in animal genetics build upon di scoveries made through the Human Genome Project, which completed a map of the human genome in June 2000. The human genome shares about 85 percent of the genes of many animals, such as cattle. That genetic overlap allowed scientists to begin discovering which genes made animals sick, more muscular or even more fertile.

Take, for example, Sygen International , which is identifying genes that allow shrimp to be raised 111

normally uninhabitable cold water.

Currently the worldwide shrimp market is worth more than $6 billion annually, accord ing to Sygen. Some 80 percent of that revenue comes from sa les in Asia, where the water is much warmer than in the United States. Another 40 to 50 percent of the total market , then, is brought back to the United States, making it the country's top seafood import.

What if the shrimp could be grown in the United States?

"That could be worth $3 billion, at least," said John Adams, the CFO of Sygen.

And because that prospect could benefit the country's trade balance, the U.S. government gave Sygen , in conjunction with the Oceanic Institute, $8 .2 million to identify the gene that allows shrimp to grow in cold water.

Considering that the consumption of pork, chicken and beef dwarf that of shrimp, many genetic research companies are looking even harder into possible applications in those markets. According to the U.S. Department of Agriculture, the beef, pork and poultry industry is roughly a $ 100 billion market.

Unti l the human genome was mapped, and with it the genomes of many animals, meat producers used complex statistical analyses to identify characteristics for selective breeding. This informat ion was usefu l for breeding but not as exact as locating speci fic genes.

Anigenetics, a Chicago-based startup, is combining genetic mapping and stat istical research to improve livestock breeding techniques.

Sygen already garners most of its revenues from identifying genes in pigs. Companies like Pyxis Genomics are also using the human genome to identify which genes in these anima ls produce, for example, more muscle (or meat) and which genes allow them to create more offspring.

Larry Schook, the CEO of Pyxi s Genomics, says that information could increase the effici ency of raising these animals by 10 percent for producers such as Cargill , ConAgro and Purdue.

Then there is the upside in preventing animal sickness, a huge cost for meat producers. Pyxi s Genomics, along with the Canadian life sciences company Inimex Pharmaceuticals, is also receiving government money -- $27 million from Canada -- to identify genes that fight diseases like E. coli, or ones that prevent infection .

"With around $5 billion sold in animal antibiotics a year, just eliminating the need for these offers enormous value," Schook said .

That doesn't include the potential value of some research on animals to humans, developments that usually come later because of the far more stringent regulatory approvals for human treatments .

636 J SCI IND RES VOL 62 JUNE 2003 SCI-TECH UPDATE

"That, of course, is a much larger opportunity,"

Schook said.

But some sure ly ask: With a ll this genet ic breeding, what will we eventually be eating?

Many contend that this type of genetic identification and cross breeding is very different from genetic modification , which is what many compan ies are hoping to do by deve lop ing so- called "t ransgenic animals" through cloning. That is when a gene from a different species is inserted into an animal, rather than just marking an a lready ex ist ing gene and trying to bring it out during the breeding process.

"Producers have been trying to ident ify what cow produces the most mi lk, for example, or which one has the best meat, and breed it -- for thousands of years," sa id Mike Fernandez, director of sc ience at the Pew Initiative on Food and Biotechnology. "This is on ly a more precise way of getting that information. "

Even so, some market observers say that consumers might find it unsettling. Regardless, genetic mapping and marking is certa inly sett ling in well with the companies themselves.

"The potential profits certain ly make it very exciting," Adams said [David Lipshultz, wirednews.com,27 December 2002].

Poison is friend-when bad chemicals make good

In 1962, Rachel Carson's Silent Spring gave noxious chemica ls a bad name. Four decades later, scien ti sts are proving that even dangerous substances can be beautiful. Once-notorious baddies such as botu lin um and thalidomide are making a comeback as researchers reevaluate the ir potential for treating other affli ct ions. Even DDT and napalm are getti ng a second look.

DDT-The chemica l was used by the military during World War II and later emp loyed as a crop protec tor and insecticide . It saved millions of li ves by helping to erad icate malaria and typhus.

Bad rep-DDT lingers in the environment, ki lling birds and fish. In 1972, the newly formed EPA banned it , cit ing health risks to humans.

Saving grace-Conservative groups like the Cato Institute say DDT can stop West Nile virus. Last year, more than 400 scientists f rom 57 countries signed an open letter to the UN call ing for the lifting of restrictions on DDT to help contro l malaria.

Botulinum-The supertoxic bacteria thrives in tainted cans, jars, and smoked food s. The toxin binds to nerve endings, preventing s ignals from reaching muscles. The result: paralysis and su ffocation.

Bad rep-Outbreaks are rare - about I 10 US cases a year - and rarely fatal.

Saving grace-Medical applications. Botox -purified botulinum - made the cover of Newsweek las t year for its wrinkle-smoothing effects, but doctors are now finding more uses: treating facia l paralys is in stroke victims and all eviating symptoms in c hi ld ren who suffer from mu scle spasms.

Thalidomide-Introduced 111 1957 by the German company Chemie Gru nen th al, it was especia lly popular for relieving morn ing s ickness.

Bad rep-It caused miscarri ages and horrific birth defects across Europe. The drug was banned world wide in 1962.

Saving grace-The FDA reapproved thalidomide for treating leprosy in 1998. It has also proven a success in fig hting myeloma, a type of bone marrow cancer. New data suggests the drug may be effective in treating lupus and in combating HIY­induced mouth sores .

Napalm-A mix of gasoline , benzene, and polystyrene, napalm was invented by US scientists in the 1940s. It burns at up to 5,000 degrees Fahrenheit.

Bad rep-After an AP photographer snapped a child running naked and burned from her V ietnamese vi ll age in 1972, the US stopped us ing it as a weapon .

Saving grace-Oi l spi ll s and diseased li vestock. In August 200 I , Nevada officia ls found that napalm destroyed anthrax-infected carcasses in just 60 minutes. In 1999, the US Coast Guard used napa lm to clean up an oi l slick a long the Oregon coast [Matthews Yeomans, wiredmagazine.colll, No. 11.01 , January 2003].

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China-the first cloning superpower

In side China's race to become the c lone capital

of the world .

I am peering into a laboratory microscope at what is sort of a c loned human be ing.

Sort of a c loned human be ing because it's only a bl astocyst, a very earl y stage embryo 'that's floating under the microscope like a tiny bit of soap foam . And also sort of becau se thi s blastocyst was created by inserting all the DNA from a human being into the

egg of a rabbit.

Thi s little swimming experiment in interspecies bio logy is taking pl ace not in some high tech office park or Ivy League research lab, but on the top floor of an emergency ward at a shabby hospital complex in mainl and China. Downstairs, the reception area is lined with battered fo lding chairs occupied by patients with makeshift bandages or open wounds. Splashed across the linoleum is what looks like dried bl ood. But here on the top fl oor, the e levator opens to a world of $ 100,000 microscopes, sperm-washing machines, and egg- denuc leating micropipettes.

Maj or sc ientific j ourna ls won't publish research that has been described in the popular media, so I have promi sed not to di vul ge identifying details about the experiment or the sc ienti st performing it, whom I'll ca ll Dr. X . But I can say that Dr. X's laboratory is one of three I vis ited in China where researchers are in vesti gating interspecies clones . And I can al so say that thi s experiment would be illic it if not complete ly illegal in the United States and most of the deve loped world. But in China it's all legal, every bit of it, which is a big reason why Dr. X moved here after spending a decade at a public instituti on in the US.

Dr X has not the slightest interest in creating an actua l c loned human be ing that will one day walk the earth . Instead, thi s researcher - like the other Chinese sc ienti sts working in the fi e ld - is pursuing a much more important goal: using spec ial ce ll s within the blastocyst to grow replacement organs and ti ssues . The cell s, ca lled embryonic stem cell s, are arguably the most important subj ec t in bio logy today, and certainly the most controvers ial. With new organs made from these ce ll s, biologists believe it will be poss ibl e to cure many ailments - and add years, if not decades, to the human lifespan.

In the Americas and Europe, tem-ce ll research is the subject of such visceral di smay - and so many government restricti ons - that it has been nearl y impossible for sc ienti sts to make progress . Things are di fferent in China. Not onl y is the fi eld less controversial, but the government is e rec ting state-of­the-art lab buildings, creating uni vers ity appointments with princely perks, and providing the capital to establi sh new biotech firms. If the current trend continues, the next great di scoveries in biomedica l sc ience - and the industries they spawn - will occur not in San Francisco and Boston but in Shanghai and Beijing.

"I loved working in the States," Dr. X says . The training, the laboratories, the equipment - all were first-rate . So were the colleagues . But because embryonic stem cell s are nearl y impossibl e to obtai n in the US , this researcher fe lt it necessary to move to China, even though it meant leaving spouse and children behind . "China, " Dr. X says, "is the future. "

Last May, more than 300 scholars and politicians gathe red at Shandong Uni vers ity, in Jinan, about 250 miles south of Be ijing, to honor the late embryologist Tong Dizhou. Above a large bronze bust of Tong hung a ceremonial banner embl azoned with the phrase : FATHER OF CLONING .

In 1963, 34 years be fore Doll y the sheep came into the world , Tong plucked the DNA from a cell in a male Asian carp, stuck it into an egg from a female Asian carp , and produced the world 's first cl oned fi sh. In prevIOus rlecades, researche rs had c loned microorganisms and nematodes, as well as amphibians, which readers of Jurass ic Park wi ll remember are genetically malleable. But before Tong, nobody had ever managed to c lone such a complex organi sm. To all appearances, the ex periment was entirely successful. The cloned carp swam around , ate its fill , and even s ired baby carp .

Ten years later, Tong inserted the DNA from an Asian carp into an egg from a European cruc ian carp , a re lated spec ies, and crea ted the first interspec ies c lone. Based on such research, Chinese sc ienti sts deve loped fi sh-breeding techniques so powerful that the nation now produces more than ha lf of the world 's aquaculture harvest. But few if any Western sc ientists knew of Tong's work, partly because he publi shed in re lative ly obscure Chinese j ourna ls; Acta Zoo logica

638 J SCI IND RES VOL 62 JUNE 2003 SCI-TECH UPDATE

Sinica, in which the interspecies cloning research appeared, didn 't even offer the English-language abst racts common in non-Western sc ientific periodicals. In any case, Tong performed his ex periments not to study cloning per se but to investigate the interactions between DNA and the egg containing it. To the Chinese, extending thi s work to humans seemed pointless. "We have a huge population problem and a one-child policy," says Qi Yaqiang, a demographer at Pek ing University (which retains Be ijing's old Romanized name). "Why would you think about making people in a laboratory?"

Attitudes toward cloning changed in November

1998, when James Thomson of the 'University of Wisconsin announced the isolation of embryonic stem cells. Five days later, a team led by John

Gearhart of the Johns Hopkins University School of Medicine made a s imil ar proclamation . Together the two stem-cell papers, one published in Science, the

other in Proceedings of the National Academy of Sciences, created enormous excitement. And suddenly, cloning - or, more precisely, one special type of cloning - seemed to have real value.

Most of the cells in the body can't reproduce themselves; instead, they simply perform their specific function until they die. Creating new cells is the province of stem cells, a distinct class that can , in the j argon, proliferate. Stem cells are located in many

parts of the body ; the best known are those in the bone marrow, which make billions of red blood cells, white blood cells, and platelets each day . When doctors perform bone-marrow transplants, they're

essentially stocking patients with new stem cell s that they hope will proliferate, creating healthy new blood

cells.

As a rule, stem cells are specialized: Liver stem cells make liver cells, retinal stem cells make retina cells. Some are less specialized than others. Neural stem cell s, for example, make three types of brain cell

and maybe even blood and muscle cells . The least speciali zed are those 111 the blastocyst, thOe

embryonic stem cells isolated by Thomson and Gearhart. Unlike ordinary stem cells, those in the early stage embryo can develop into every kind of cell in the body: nerve, stomach, bone, you name it.

Ultraviolet rays spill into the scrub room 111

Deng Hongkui's research garage in Beijing.

In theory , doctors should be able to manipulate embryonic stem cells to grow lungs, live rs, hearts, or any other tissue, which could then be transplanted into people who need new organs. Because this process begins with DNA from a patient's ce ll s, it's c loning, except that what's being created isn't a whole human being, but pieces of one. In the short run , thi s special kind of clon ing - therapeutic , as opposed to reproductive - could make transplants far more feasible. In the long run, it could open a new medical era in which doctors regenerate people as they age.

There's a catch, though: Embryonic stem cells can be obtained only from human embryos. These can e ither be made to order in a lab by inserting a patient's DNA into an egg and producing a blastocys t that is a c lone of the patient, or else take n from aborted fetuses or embryos left over from in vitro fertilization . Neither source is free of controversy , to put it mildly. Cloning of either type is opposed by such powerful entities as the Roman Catholic Church , the right-to­life movement, the president of the United States, and Jeremy Rifkin . Even fi ercer is the battle over embryonic stem cells from abortions or in vitro fertilization. Much of the West finds the thought of using either source repellent, and legis latures have raced to outlaw the entire field. Last year, Pres ident Bush banned the use of federal fund s for creating new embryonic stem cells. For its part, the European Union has imposed a moratorium on fundin g the creation of new stem cells and prohibited the use of existing stem cells in most research .

Private enterprise isn't filling the gap. Learni ng how to use embryonic stem cells to grow organs will require the kind of long-term, basic research that few companies are willing to undertake , espec ially when throngs of angry demonstrators could be involved. PPL Therapeutics, the firm that bankrolled Dolly, got out of the cloning business in September; Geron , one of only two US-based companies to admit researching embryonic stem cells, has faced so much politica l pressure that its investors are running scared and capital is drying up. "Nothing is happening," says James Michael Weimann , a stem-ce ll researcher at Stanford. "The field is moving at a crawl. We can't get our hands on the materials we need, and neither can anyone else."

Across the Pacific, though , public opposition to stem-cell research is weak or nonexi stent. In Singapore, stem cells are a key part of a long-standing

SCI-TECH UPDATE J SCIIND RES VOL 62 JUNE 2003 639

government Il1ltJatl ve to develop new technology industri es; Japan is building a stem-cell center in the southern c ity of Kobe that will have a $45 million annual research budget. South Korea's government endorsed experimentation with frozen embryos thi s summer, though it banned the c loning of human beings after the Rae lian sec t, which attributes Jesus' resurrection to "an advanced cloning technique," claimed it had implanted a cloned embryo into a Korean woman.

No country is pursuing the field more aggress ive ly than China. Stem-cell research fits the Chinese Mini stry of Science and Technology's ambiti ous plans to vault the country to the top research ranks - and win a Nobe l, which has never been awarded to scienti sts on the mainland . China has turned on the funding spigots, pumping money through multiple sources: Cities, provinci al governments, two spec ial national research initiati ves. There are also venture capital-like funds from large uni versities, which set up companies owned by their researchers; national subsidies, including those establi shed to create special research parks; and direct private investment, most of it from Hong Kong tycoons. US venture capitali sts have also begun sniffing around.

Flush with cash, researchers can explore the new field with almost complete freedom. A Ministry of Science and Technology pane l has begun to consider rules for supervising stem- cell research , though nobody knows if or when these rules will emerge. For now, the sole national regulation in the field is what scientists call the Four Nos - a single­sentence direc tive promulgated by the Ministry of Health last November: "Under no situation, under no circumstances, will human reproductive cloning experiments be I ) endorsed, 2) permitted, 3) supported, or 4) accepted." Everything else is fair game. And even the Four Nos are toothless, because Mini stry of Health rules don't apply. to the other branches of the government that are actually funding the research .

One of the world's fastest-growing and most important stem-cell centers is a converted garage located on the campus of Peking University . Tacked to the front door, a handwritten sign claims the lab is a storehouse for samples of the AIDS viru s. "Keeps

away random visitors ," ex plains Deng Hongkui , co­director of the faci lity.

Deng's facility has been s lapped together Silicon Valley-style by carving up the garage into a warren of glassed-in cubic les c ri sscrossed by improvised ductwork and wiri ng. Deng himself has an office smaller than Larry Ellison's desk . When my translator

and I sit down, Deng boots up the Universal Scientific Tool: PowerPoint.

Ambitious and fin anciall y sophi sticated, Deng is a paradigmatic example of the scienti sts China has lured back to work on stem-cell research. Raised in China, Deng obtained hi s PhD in immunology in the

United States. In 1996, he led a New York University team that was one of the five groups to

simultaneously uncover the exact biochemical pathway by which the AIDS virus enters ce ll s. The finding was Science magazine's "breakthrough of the year." Having made hi s reputation, Deng did what a lot of other bri ght young scienti sts do these days: vani shed into the pri vate sec tor. He couldn 't talk

about his work there with anyone - he could barely acknowledge it. Frustrated, Deng did the unthinkable and moved back to China .

Between 1978 and 1998, according to the semiofficial China News, China sent more than 380,000 students, the great majority in sc ience and engineering, to earn advanced degrees in countries in the West. Fewer than one out of three returned - a textbook example of brain drain . "Read any issue of Science or Nature, and I would be very surprised if you could find one without [articles written by] overseas Chinese," suggests Cao Cong, a soc iologist

at the Nati onal University of Singapore. In Cao's

view, the thousands of overseas Chinese scienti sts play a bi g but little-known ro le in the West's technological dominance. "Now China is beginning to take real steps to lure back its children. If they return , it will be a very big blow to America and Europe."

Zhao Chunhua (right), with a technic ian sorting ce ll s for analysis, worked on stem cells in Minnesota before returning to Tianjin.

If Deng is an example, the West should worry . When he returned in 200 I , Peking University gave him and hi s co- director Ding Mingxiao a budget sufficient to pay 40 grad students and postdocs

640 J SCI IND RES VOL 62 JUNE 2003 SCI-TECH UPDATE

enough to make them think twice about studying

abroad. Foreigners can freely visit their laboratory, in

strik ing contrast to prior restrict ions. (In fact, the constraints on inte ll ectual exchange are now tougher

in the US ; after September II , Chinese scientists are

frequently denied visas .) The university will help

Deng commercialize his discoveries , potentially making him a rich man . "The administrators here are

very supportive," he tell s me in fluent English . "They

just bought me a $380,000 cell-sorting machine. And

they're making us a real building" - a multistory

facility now under construction at the edge of the

campus. "1 couldn't turn down the opportunity to have

my own laboratory," he says. "Besides, I don't know

if you've noticed , but this city is full of really good

Chinese food."

Given the opportunity to work in almost any area, Deng decided to investigate the means by which stem cells differentiate, transforming themselves from the biological equivalent of blank slates into cells of particular types and abilities. "What signal tells them to do thi s?" Deng says. If the cells are to be harnessed,

doctors must identify the molecular signals - the

programming factors, as they are known - that command them to differentiate. According to Deng, hi s group has already discovered five of these factors. "We have several quite exciting stories," he says.

When Deng tells me this, it's close to midnight. He's leaving the next morning to see a lawyer in New York. "Patents," he says. "I have to get that st raightened out first." It is widely believed that, in the future, companies will be pumping out streams of tissue and organs from stem-cell banks. When that happens, Deng hopes, they'll have to license his programming factors. If his discoveries work, it will be like controlling the rights to X rays. Only when he controls the technology will he submit a paper to Science or Nature.

"The Chinese used to not understand intellectual property," Deng says. "But now I really think they get it."

The confucian tradition

Before Confucius, China had four great sages.

You Chao showed the people how to avoid wild animals by making tent houses in the trees . Sui Ren brought fire. Fu Xi taught how to makenets and raise livestock. Shen Nong introduced the plow and agriculture. All of this is legend, but every Chinese

person knows it and gets the poin t: The sages gave

China the technology to control Nature. Which to this

day - or so it is widely argued - accounts for the enormous respect given to sc ienti sts in China. And

which in turn explains why the Chinese aren't

dismayed when their sc ientists expe riment with human embryos.

In the Confucian tradition , human beings achieve personhood only when they're able to participate in society. By thi s way of th ink ing, fetuses

aren't human - they're part of Nature. And because

Nature, in turn, is regarded as the raw material for human existence, people can do with fetuses what

they will. "Abortion, which destroys embryos, has

never been seen as wrong in Chinese society," says

Qi, the demographer. "Not having a mal e heir - that is an issue."

As a consequence, the Chinese government has

adopted a position regarding ste m-cell research, therapeutic cloning, and regenerative medicine that might be described as brutal rea li sm. Beijing

recognizes that some people are goi ng to do stupid

things with the technology, poss ibly even cloning

themselves. But the Chinese aren't concerned enough by this prospect to ban the research outri ght.

In fact , Chinese scientists are counting on the West's cultural revulsion to build their lead. Consider

Huang Shaoliang, who was so sure the West would take itself out of the stem-cell race that he thought he

wou ld make Nobel-worthy advances in hi s outdated lab in the southern city of Guangzhou. A researcher at

Sun Yat-Sen University, Huang spent the early 1990s studying umbilical-cord blood , which is teeming with stem cells. In theory, injecting patients with the blood from infant umbilica l cords should be better than transplanting bone marrow, because umbi I ical-cord stem cells are less likely to transmit infectious diseases, are collectible without surgery, and seem to

be less differentiated. Cord blood is difficult to use, however. As a practical matter, the only cord blood

that can be transplanted Ento patients without rejection is from siblings. Usually , patients can get cord blood only if their parents have another child. In most cases, this is hardly possible; in China, with its

one-child policy, it's especially diff icult. So Huang decided to investigate a substitute for cord blood : embryonic stem cells.

SCI-TECH UPDATE J SCI IND RES VOL 62 JUNE 2003 64 1

At the time, Western researchers we re ex tracting embryonic stem cell s from mice and trying to differentiate them into blood cell s. Huang wanted to do the same thing with humans. He knew that working with human embryos in the West was d ifficult at best, illegal at worst. But the Chinese research environment , Huang dryly observes, "i s not as strict."

In 1995, the Nati onal Sc ience Foundati on of C hina gave Huang money to in vesti gate human embryoni c stem cell s . The Sun Yat-Sen medical schoo l had an in vitro fertili zati on clinic, and after impl anting the best embryos in patients, it simply let Huang have the leftovers .

By the end of 1997, Huang and hi s chief graduate student , Xu Ling, thought they had isolated embryoni c ste m cell s, though they were able to keep them ali ve for onl y six generations. To check the ir results complete ly, they needed to run ce ll s through multiple tes ts. But they couldn't perform the newest, best tests, which looked for the presence of spec ific chemical markers on the surface of the cell s, because they required special reagents made to order by uni versity- affili ated companies in the Wes t. The reagents aren't ad verti sed ; they c ircul ate by word of mouth in the sma ll community of researchers. Huang, who speaks no E ngli sh, couldn 't find what he needed .

In new government buildings and pri vate firms li ke Uni on Stem Cell & Gene Engineering Co., Chinese researchers are developing the means to clone organs in everything from humans to pandas; clinical tri a ls could begin by nex t year.

Huang asked Xu, who knows some Eng li sh, to beg for the compounds fro m a Western sc ienti st. Xu chose James Thomson, whom she had never met, but whose work on primate ste m cell s she admired . Using the email address provided on a sc ientific paper, she sent Thomson what she call s "a very deta iled account" of the ir methodology and results, asking if he woul d he lp them obtain the reagents. Thomson d idn 't respond .

In Janu ary 1998, Huang, Xu , and fo ur other coauthors publ ished "Diffe rentiati on and Pro l ife ration of Human Embryonic Stem Ce ll s" in the Journal of the Sun Yat-Sen Uni vers ity o r Medical Sc iences . Because the j ourna l is sma ll and written in C hinese, the study was almos t complete ly ignored. E leven month s later, Thomson created worldwide headlines with hi s Sc ience arti cle about e mbryoni c stem cell s.

Thomson's paper, Huang concedes, was "beautiful - much better than ours." But he says that its appearance was "very surpri s ing." It had never occurred to him that an American scienti st would be permitted to work on embryos - and , in fact, Thomson was forced to set up a separate, pri vate ly funded lab to do so. Until I contacted him, Th omson says , he had never heard of Huang or hi s work. But he thin ks Huang "may well have succeeded" in iso lating embryonic stem cell s. The re lati ve ly bad conditi ons in Guangzhou may have posed no proble m; Thomson's own makeshi ft ste m-cell lab, he notes, was "poorly equipped," with "a culture hood, an old microscope, and a c linical centrifuge and not much e lse. "

Pres ident Bush's effort s to ban c loning "came too late," Huang says wryly. But now that stem-ce ll research has almost stopped in the West, "I should have another chance" to make a maj or d iscovery. T he onl y problem is that the uni ve rsity in vitro c lini c, sme lling opportunity, won't g ive him any more embryos. "They want to expl o it the m fo r themse lves ," he says. "They don't want to share."

In the I 920s, a young sc ienti st named Lu Huili n spent two years working at Co lumbi a Uni versity under T . H. M organ, arguably the century's greatest geneti c ist. Upon his return , Lu became a prominent exponent of the gospe l of evoluti onary bi o logy, even translating Morgan's class ic Theory of the Gene . But hi s e ffo rts were undone in the 1950s, when the Chinese government embraced Lysenkoism, a doctrine that cla imed Darwini sm was wrong because it contradicted Marx. Lu stepped out of public life, but his youngest daughter, Lu Guangx iu , decided to fo ll ow her father into medi cal researc h. Aga in , po litics intervened. Tn 1966, two years after Guangx iu graduated, M ao unleashed the Cultura l Revoluti on. Because even the Red Guards woul dn't attack hospitals, she took a j ob as a surgeon.

In 1980, after the Cultura l Revoluti on had ended, the middle-aged Lu j o ined X iangya Medica l Uni vers ity in C hangsha, the gritty south-central fi yover city where her father li ved (" I am a C hinese daughter - I had to take care of him"). At the time, the school had littl e money for sc ience. To pay fo r her research, Lu opened C hina's first in vitro fe rtili zat ion c linic . She did a ll of the work herse lf, even bas ic

642 J SCII ND RES VOL 62 JU NE 2003 SCI -TECH UPDATE

tasks li ke bo iling water. Four years afte r the clinic opened , her father wrote Human Reproduction and Reproduc ti ve Engi neering, a textbook that predicted the advent of c loning (he di ed in 1997). Today, his daughter carries on his work. A lthough not we ll known outs ide Changsha, Lu's operat ion has grown into an important center fo r human stem-cell resea rch, partl y because of her determination ' - and partl y because the c lini c supplies a ll the froze n human eggs and embryos she needs.

Because IVF frequentl y fa il s, clinic ians use drugs to induce super-ovul at ion, producing 10 to IS eggs at once. T he eggs are harvested and pl aced in a bath o f sperm . After the eggs a re fe rtili zed, Lu picks the most viable zygote in the bunch, and implants it. She keeps the rest in tanks of liquid nitrogen the s ize and shape of pony kegs. Afte r two years, if the patient has g iven bi rth to a healthy baby, Lu offers the parents a cho ice: The leftover embryos can be destroyed , g iven to infe rt ile couples, or donated to sc ience. Mos t c hoose the last option. U ltimate ly, Lu says, she ends up with "a few tens of embryos every year that are usable ."

T hat number is bigger than it sounds . T he US has at leas t I 00,000 surplus frozen embryos in its hundreds of IYF c linics, but none of them, practica ll y speaking, can be used for research. As a result, US uni ve rsity sc ienti sts now have onl y .fi ve lines of stab ly reproduc ing cells that they can work with, accord ing to the A merican Society of Reproducti ve Med ici ne. (A few pri vate companies a lso have stem­cell lines, but they a ren't ava ilable to outside resea rchers.) Lu, who was able to learn her trade on countless mice and 30 to 40 human embryos, says she has three lines firmly establ is hed, just two fewe r than are pu bli c ly ava ilable than in the entire US. She's testing another fi ve or six.

To contro l stem cell s for human benefit, sc ientists need to deve lop what they someti mes call fingerspitzengefii h l, a German te rm that could be trans lated as "knowledge of the fingertips" - the combinati on of ex perience and intuiti on that indicates prec ise ly when to jiggle the dish or turn down the heat to assure the right result. The onl y way to acq uire thi s ex perti se is to make lots of mistakes w ith actua l eggs and embryos. Researc hers without access to froze n eggs and embryos can't develop any of the necessary hands-on experti se. Lu , who has freezers full of them to herself, has a s igni ficant ·ad vantage.

F ingerspitzengefuhl is important because

embryonic stem cell s are tricky to work wi th . T hey

exist sole ly in a specia l inner porti on of the b las tocys t

and are only totipotent - able to tran form themselves

into any kind of ce ll - between the four th and seventh

day afte r the egg is fertil ized. In th labo rato ry, they

are d ifficul t to mainta in in the ir totipotent stare,

because they constantl y seek to d iffere ntiate

themselves into normal, dead-end ce ll s . T he most

wide ly used method fo r keeping ste m cell s alive

in volves grow ing them in petri dishes atop thin sheets

of mouse embryo cell s, in a goo made fro m cow­

blood serum. To test the ce ll s, researc hers inj ect them

into mice that have been genet ical ly engi neered to

have a lmost no immune system (with out immune

systems, the ir bodies can't rejec t fore ign ti ssue). If the

stem ce ll s are to ti potent , they will grow inside the mice and di ffere nti ate the mselves into bi za rre tu mors

cal led teratomas, c lumps of tissue that appear where

they don't be long. M ost are j ust jumb les of f les h, but

recogni zabl e ha ir, teeth , eyes, and even enti re t iny

skele tons can a lso appear. Be ing a stem-cell

researcher frequent ly in vo lves p lucki ng min iature

human ti ssues fro m the cadavers of mice.

"W e have a huge populati on and a one-chi Id

po li cy. Why would you thin k about mak ing people in a laboratory?"

All over C hina, stem-cell researc hers a re

carving up the field into chunks and attack ing each

one. Deng, with hi s well -supported operati on in

Be ij ing, is examining how the body di rec ts stem cell s

to diffe rentiate. Lu 's large ly self- fu nded group is

tackling half a dozen problems at once . In add iti on to

c reating new lines o f stem cells, he is al so look ing at

the bas ics o f c reati ng the embryos that produce the m to begin with . The Changsha researchers are taki ng

the DNA-filled nucleus fro m an adult ce ll , "de­diffe renti ating" it to reprogram the DN A to its fe ta l

state, inserting the resu lt in to an egg, and formi ng blas tocys ts - the first steps toward therapeuti c c loning. (The embryos are frozen or destroyed afte r study .)

In thi s manner, Lu says her team has c reated more than a hundred c loned e mbryos. T hey will need to make many more before they can c la im to have mastered the process - before c loning becomes routine. Still , Lu says that they have a lready made

SCI-TECH UPDATE J SCI IND RES VOL 62 JUNE 2003 643

major advances. "Five percent of our attempts form blastocysts," she explains. "That's better than any

place else I know."

Some Western critics sco ff at the claims of

Chinese stem-cell researche:'s, many of whom have

yet to publi sh the ir work. In a recent report, the US embassy in Beijing warned against researchers

making "fa lse claims simply to ' draw media attention ." In part, the skepticism comes from cultural

arrogance. But at least some of it is justified, due to

what mi ght be called the Xu Factor.

Xu Rongxiang has an office in the Beijing

Hotel, a half-dozen old buildings in the city center

that have been g lued together, end to end, into a massive marbl e bricolage hundreds of yards long. Suite 530 I , from which Xu runs hi s empire, is so

private that the hotel reception doesn't even know it exists - my trans lator has to call Xu from the lobby

telephone to ask directions . Xu directs us to an unmarked elevator, where we meet one of hi s subordinates. Upstairs, the office is dominated by

Xu's desk and Xu himself, brilliant in a gray double­

breasted sharkskin suit. We're here because, last August, Xu made the astounding claim that he had cloned 55 organs and ti ssues - an announcement that

caused a media sensat ion in China.

In the inevi table PowerPoint presentation, Xu shows us merc ifully blurry photographs of people with horrible burns all over their bodies. The

conventional treatment for burn victims is skin grafting, a method that keeps people alive but leaves

them with scars and permanently frozen joints. Back in the 1980s, Xu got the idea of smearing their

wounds with gunk made from traditional ingredients like Baikal skullcap root and Chinese cork tree bark -

a method , Xu tells us, that had incredible success. An hour into the pitch, his proof shows up in the form of Shi Yufa, 44. Shi walks into the hotel suite and immediately doffs hi s clothes to reveal a perfectly ordinary torso. At Xu's insi stence, I palpate Shi's skin to feel the absence of scars. Meanwhile, Shi

brandishes a ghastly photo of his burns.

Soon after, Xu moves his caravan - Xu , me, our

respective translators, and a couple of Xu's minions -from the hote l to a dinner theater in a plush

ne ighborhood. We sit in the center of the front row as

barely dressed young women reenac t hi sto ri cal

tableaux in a style that might best be characterized as

Late-'70s Oscar Dance Number. Meanwhile, Xu tells me about his stem-cell breakthroughs. The gratitude

of thousands of former burn victims , Xu exp lains, led

him to found MEBO Group, which se ll s Xu's

patented burn ointment and various cosmetic fluids. It also led him to make revo lutionary advances in stem­cell research. Every part of the body, he says, has a

few "potential regenerative cells" tucked ins ide. In

other words , a smattering of embryonic ste m cells

remains in our tissues even as we grow old. By isolating and stimulating them, Xu promises, he'll be able to clone 206 organs and tissues within five years.

To back up hi s claims, Xu presents a slick, co lorful press release head lined "CHINESE SCIENTIST

REVEALS THE MYSTERY OF LIFE."

In itse lf, the notion that some embryonic or very

early stage stem cells might survive to adulthood is

not crazy - Pei Xuetao, director of the Beijing

Institute of Transfus ion Med icine, is looking for more

or less the same thing in his research. But Xu's

hypotheses weren't why a dozen high-profile

scientists publicly denounced him in September. In China, Communist party functionaries control

research funding, and researchers fear that they can

be too easily swayed by the promises of charlatans.

The obvious example is Trofim Lysenko , who gained

support by guaranteeing miraculous agricultural

advances to the credulous Russ ian government ; his

Lysenkoism movement set back Communist-bloc

biology by two decades. Xu has already won backing

for his amazing burn therapy from the Chinese

government, which has set up 4,500 hosp itals to

practice his methods. Now he's looking for new

worlds to conquer. The prospect of people like him -

hypermodern, commercially minded, media-savvy

versions of Lysenko - is "very worrisome," says Pei Gang, director of the Chinese Academy's Shanghai Institutes for Biological Sciences.

Over the years, Pei says, "many people have

done similar things, either for commercial reasons or to obtain funding." The public attack on Xu was a

first attempt by scientists to fight back. "They've been successful in the past," Pei says. "We must be on guard."

644 J SCI IND RES VOL 62 JUNE 2003 SCI-TECH UPDATE

Ultimately, the acme of stem-cell research is organ transplants without donors - the poss ibility that

one day heart-attack patients will rece ive glistening new c loned hearts from a tray. If thi s is achieved, it

will transform human life . And as the Chinese know, bi g changes lead to big fortunes; they want

tomorro w's biotech tycoons to speak Mandarin .

In a ll like lihood , the therapeutic cloning of the

fu ture will invol ve what is known as autologous

transplantation: nipping a dot of flesh from a patient's inner arm, sucking out the DNA from a fe w cells, de­

diffe rentiating the genetic material into the embryonic

state, in serting it into eggs and creating blastocysts ,

then using those cel ls to clone new hearts from the patient's own DNA. Doctors perhaps one day will be

able to grow some organs directly from adu lt stem cell s, bypass ing the e mbryo stage, but this is an even

more di stant poss ibility . For now, sc ientists have only

c rea ted blastocysts in the lab and are just beginning to unrave l the myste ries of de-differentiating the stem

cell s inside.

Jumping the re mall1l11g scientific hurdles will

not be easy. If therapeutic c loning is to become

widespread, for example, doctors wi II need huge

numbers of human eggs. Alas, extracting eggs from women is painful, costly , and unreliable. Even if large

numbe rs of eggs somehow become avai lable, many

sc ienti sts be lieve that de- diffe rentiating adu lt DNA back to its feta l state degrades genetic material , which may exp lain why many of today's cloned animals

have health proble ms.

Chinese sc ientists are attacking both problems.

To avoid the need to take huge numbers of eggs from

women , Dr X is trying to create blastocysts from

rabbit eggs. This is not as crazy as it might sound. As the DNA in the zygote d ivides, it creates new cells -

that is, the embryo - inside the egg wall. Eventually, these ce ll s take over the deve lopmental process from

the egg. In other words, as the human DNA in Dr. X's ex periment produces new cells, the embryo will lose

a ll traces of its rabbit origin.

To attack the second probl em, scient ists must tri ck the immune sys te m, which recognizes invading

ce ll s by samp li ng their surfaces for chemical signatures called HLA marke rs. An individual's

collection of HLA markers IS a bi t like an immunologi cal fingerprint - except that fingerprints

are unique, whereas HLA markers are thought to have

up to 100,000 combinations. It shou ld be poss ibl e to build banks of stem cell s that have every co mbinati on

of HLA marker and with them produce organs that would evade rej ection .

Han Zhongchau and Zhao Chunhua are working

toward estab li shing such a bank. A n intense, stocky man with rimless g lasses, Han spent I I years in Paris

before the Chinese Academy of Science rec ruited him

to run its Institute of Hematology in T ianjin , China's fourt h-l argest c ity; Zhao, who worked at the

University of Minnesota's hi ghly regarded stem-cell

lab, is hi s chief investigator. Tianj in researchers have

iso lated adult stem cells from "pretty much every

tissue of the body," Zhao says , and are lea rning how to guide them into developing cloned organs and

tissues. They hope to be in early c linical trial s in one

or two years.

Like Deng in Beijing, Han is getting a brand­new building from the government. Besides thi s, he

has three private ly funded buildings in a research

office park at the edge of town, plus a columnar, nine­

story structure with a big green marquee s ign that

reads UNION STEM CELL & GENE ENGINEERING CO.

Among the severa l programs at Uni on Stem Cell

is a kind of pilot project for tomorrow's stem-cell banks. Under Han's direction, everyone of the SO-odd hospital s in Tianjin is sending umbilica l-cord blood

from the babies born in its childbirth centers to a

cord- blood bank funded by the China Medical Board of New York, an independent fou ndation . The cord­

blood bank identifies the HLA markers and freezes

each cord- blood samp le for future use. For s imilar reasons , the US has a lmost SO cord-bl ood banks, including the world's oldest and bi ggest, In Manhattan. Established 10 years ago, the New York fac ility has 18,000 samples. The bank in Tianjin , in operation for just one year, a lready has 6,000. "We'll

pass New York soon ," Han says. Eventually, the Tianj in bank plans to have 500,000 cord-bl ood

samp les. "There are advantages to li ving in a trul y big country."

With a limitless supply of eggs and stores of frozen stem cell s, autologous cloning could become

SCI-TECH UPDATE J SCIIND RES VOL 62 JUNE 2003 64S

as common as bypass surgery - but with far greater

impact. Suc h claims, frequently heard from stem-cell

supporters, may sound abstract, even glib . But they aren't, as I was forcefully reminded when I visited Li

Linsong, direc tor of Peking University's Stem-Cell

Research Center.

A trim , energeti c man, s leek in black knits, Li

is so ebulli e nt about hi s research that the postdocs

he summons to ex pl a in the ir work can ha rdly get a

word in. As he g ives us a ride in hi s plush new cm,

ce ll phone consta ntl y c hirpin g, I can eas il y imag ine him as c hi e f sc ie nti st at a well-financed startup in

Silicon Valley. Li spent a lmost a de~ade working at Stanford and the University of W as hington , re turnin g to China in 2002. The opportunities bac k

home for a young scienti st, he te ll s me, were

imposs ibl e to turn down . In additi on to c reating th e

stem-ce ll center for hi s team, the univers ity a lso

set up SinoCells Bi otec hn o logies, a publi c-private

partne rship inte nded to commercialize Li's researc h.

In Be ijing, Li runs half a dozen scientific teams concentrating on two areas of research , one of which

is the creat ion of neural stem-cell lines. In as-yet

unpubl ished experiments, Li and his collaborators dropped weights on the backs of rats, breaking their spines - a lab-mode l version of the injury suffered by

actor Christopher Reeve. Afterward, the rats were

unable to walk. Then the team inj ected human stem

cell s into the ir wrecked spinal cords. Within days, Li says, the nerves regenerated.

Li describes hi s work with proper sc ientific dispassion , but hi s words make the ha irs on the back

of my neck stand up . Years ago I visited a spinal­cord injury ward. Accident victims lay motionless in

the ir cots , faces racked with pain , watching me and

the doctor I'd come to inte rview walk eas ily around

the room. Out of earshot of hi s patients, the doctor sa id , "We can't do a damn thing for the m except

treat their bedsores." I imagine the conce ntrated suffering in that ward di ss ipating like smoke as Li shows me videos of the hea led rats circling about their cage, two o r three c raw ling over and under one

another at a ti me.

Li 's work may not be verified. Like much of the research I saw in China, it's unpublished and might be wrong - in science, it's easy to fool yourself. But the

odds of all the stem- cell research in C hina not producing anything of value are miniscule. And even

if only a small percentage works out , so much is happening that China will still shape our medical

future. "We a lso have some interesting stem-cell results with Parkinson's di sease," Li says, the li ght

from the video flickering on hi s face. "I believe many

things will happen, and they will happen here." All

the while, the miraculous rats climb obli vious ly around the ir cage [Charles C Mann ,

wiredmagazine.com, No. 11.0 I , Janu ary 2003] .

Carbon nanotube elevator

Nanotech's promise is out of thi s world. Just ask Brad Edwards, who's planning to build a carbon­nanotube elevator that goes 62,000 miles straight up.

Of all the revolutionary technologies just ahead, nanotechnology seems the most outlandi sh. M achines the size of molecules made from material s stronger than titanium, se lf-assembling compute rs smaller than bread crumbs: We've heard the hype about such microscopic marvels for a decade, but it's st ill kinda hard to be lieve.

The nuts and bo lts are familiar. Nanotubes, bonded-carbon cy linde rs mere billionths of a meter wide, are hi ghl y res istant to tension, heat, and decay. Woven into fibers, nanotubes could create a fabric potenti ally hundreds of times sturdier than stee l, and a fifth the weight - the strongest mate ria l ever found on Earth .

Photo: Michael Elins; Illustration: High lift Systems; Background: Getty Images

646 J SCI IND RES VOL 62 JUNE 2003 SC I-TEC H UPDATE

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Or off. Li sten to what Brad Edwards suggests doing with the th ings . The founder of Seattle-based Highlift Systems, Edwards proposes a carbon­nanotube space e levator: a ribbon 62,000 miles long, 3 feet w ide, and thinner than the paper your thumb is pressed against ri ght now. The e levator would stretch high into the heavens, allowing easy transport from Earth, launching spacecraft , new industries, even tourists - at a fraction of today's costs. And he says he can be well under way in a decade, ushering in a new era of space ex ploitation.

For all its revo lutionary potential, the space

elevator is an o ld idea. In 1895, Russian scientist Konstantin Tsiolkovsky looked at the e levators

ascending the Eiffel Tower and dreamed of a "celestial castle" ti ed to Earth. In 1979, Arthur C. Clarke's nove l Fountains of Paradise concerned a supercarbon e levator that produces great change and

not a little chaos.

Twelve years later, in a research lab in Japan , sc ience surpassed the sc ience fiction . Experimenting

with soccer ball-patterned carbon cages called fullerenes, Sumio Iijima noticed a sooty-looking byproduct. Looking at the res idue under an electron microscope, lijima found that the fullerenes had transformed into tubul ar graphite structures with a remarkably strong lattice of walls . A flurry of research showed that these carbon nanotubes, as they came to be called, were able to conduct both heat and

electricity . From Los Alamos National Lab, a young Brad Edwards kept close watch with more than idle curiosity. He was heading up an i11- fated plan to explore Europa, one of Jupite r's moons, and impossibly high transport costs had just grounded the project. "I started thinking that if I was ever going to get up in space," Edwards says , "I'd have to do it

myse lf." With the nanotubes, he reasoned, he just

might make it.

Edwards had al ready won a virtuoso's reputation at Los Alamos for thinking differen tl y. Many told Edwards that hi s idea for an optical refrigerator -

which keeps machines from overheating by us ing lasers to coo l a specia lized form of glass - defied the laws of thermodynamics. T he concept had been

around since the 1920s, but prev ious lasers only melted the glass. Edwards' team developed a precisely

tuned beam that, paradox icall y, absorbed the heat it produced and more. After two years of work, they

created a prototype, beating other researchers, including a Nobel physici st, to the punch .

In 2000, Edward s left Los A lamos for Eureka Scientific, a research group fo r NASA grant proposals . Two years late r, he set up Highlift in downtown Seattle. On a recent day in hi s small office there, Edwards holds up a bl ack st rip 2 feet long. It' s a prototype of the ri bbon , hundreds of

hairlike fibers strung togethe r to di stribute tension. The strip represents what could be Hi ghlift's first

commerc ial product, a nanotube compos ite four times stronger than steel. When it hi ts the market, it could be used to , for example, make superstrong tennis rackets, create cars and pl anes th at are at once lighter and sturdi er, and add decades of durability to infrastructure proj ects like bridges o r freeways. Within two to three years, Highiift should have a material strong enough for the space elevator

ribbon.

The elevator itself will be built upon something resembling an offshore oil platform (way offshore: Highlift is looking at a s ite in the eastern Pacific, 1,000 miles from the Gahipagos Islands). Construction would start with expendable rockets (such as the Delta 4 or Atlas 5) shooting into low Earth orbit. There, the rockets will link up, creating an 80-ton spacecraft that will ascend to 22,000 miles and lock into geosynchronous orbit.

SCI-TECH UPDATE J SCI INO RES VOL 62 JUNE 2003 647

From there, the craft will unreel the ribbon 40,000 more miles into space, and lower a weighted

ribbon to the ocean platform (centripetal force will do most of the work getting it up ; gravity will help get it

down). Edwards estimates that the ribbon will land within 100 miles of the platform; a GPS locator and beacon on the ribbon's end will help a ship retrieve it and attach it to the platform.

With a counterweight attached at the far end, the strand wi II stay taut through sustai ned centripetal force. Now comes the heavy lifting : 7-ton climbers, each the size of a semitrailer, will

ascend the ribbon at 120 miles an hour, carrying payloads weighing as much as 13 tons . The climbers will be powered by earthbound free- electron lasers , which is the same tech behind Stanford's linear accelerator. The lasers are aimed at photocell s on the climbers' undersides, the photocell s power the climbers' motors, and the elevator goes up. Edwards reckons it will feel like taking an elevator in a tall building. In a few hours, you'll reach outer space. In

two weeks, you'll reach the ribbon's end - one

quarter of the way to the moon.

The economies of scale behind the space e levator could make a trip into space as mundane as a trip to Maui. Launching a pound ' of cargo by rocket or space shuttle runs about $40,000. Edwards figures the space elevator can do it for $200, a figure that could drop to $10. Go weigh yourself and multiply.

In short, Edward's lift could do for the new

century what railroads did for the 1800s: slash the cost of a ticket to the new frontier. Outer space is suddenly a lot closer than we think.

Every time the 39-year-old Edwards presents hi s project, scientists pelt him with the same question s. He answers each with the equanimity of a parent explaining why the sky is blue. What if an airplane crashes into the thing? (Doubtful, given a base 400 miles from the nearest air route.) What about a terrorist attack? (There will likely be military protection.) Lightning? (Few storms strike in the area.) A meteorite? (Like a spacecraft, the material will just need to be strong enough to take it.)

A platform in the Paci fc wi II serve as the

anchor for Highlift' s 62,000-mile ribbon of carbon­

nanotube composite. Earthbound free-electron lasers will deliver 2.4 megawatts of power to ga llium­arsenide photocells on the underside of 7-ton

climbers. That propels a series of traction- drive rollers that pinch their way up the ribbon. Carrying payloads up to 13 tons , a climber can set satellites or solar cells in orbit, send modules to an airlock on

the International Space Station , or fling spacecraft into the solar system.

Edwards' patient explanations are paying off. He's received $570,000 from NASA's Institute of Advanced Concepts program, which funds experimental projects, and hopes for more from

Darpa and the Air Force. Highlift expects private investors to put up much of the $40 million for its composite. Later, the company will pass the hat again, for $7 billion , to build the elevator itself.

The space elevator remains a dream. But like many things nanotech, it' s a dream that could

happen - and indeed change the way we live. "If you start putting people, factories, cities into orbit cheaply, it would have a profound effect on every

aspect of human life," says Harley Thronson, technology director in NASA's Office of Space Science. "Humans would occupy a three­dimensional world, rather than the two-dimensiona l

world of Earth's surface." The gateway to that dimension may be as small as a ring of carbon molecules.

10 years of nanotechnology

1995

White House science adviser Jack Gibbons calls nanotechnology "a powerful economic engine" and urges further research .

1996

Richard Smalley, Robert Curl, and Harold Kroto share a Nobel for finding supercarbon fullerenes , aka buckyballs.

648 J SCIIND RES VOL 62 JUNE 2003 SCI-TECH UPDATE

1997

Nadrian Seeman at NYU develops the first DNA-based nanomechanical device.

1999

Cees Dekke r of the De lft University of Technology designs the first carbon- nanotube

tran s istor.

2000

US launc hes the National Nanotechnology Initiative, inves ting $270 million to fund nanoscale sCience.

Carlo Montemagno and other sc ienti sts at Cornell create the first nanomachine, a motor connected to a propeller.

2001

IBM and other outfits make mol ecular-l ogic circuits entire ly from nanotubes, a major step toward carbon chips.

2002

NASA Ames Research Center builds a latticed nanostructure from modified microbial proteins [wi redmagazine.com, issue 11 .04, April 2003].