This year's Nobel Prize in medicine went to a trio of scientists who discovered the enzyme telomerase, which allows cells to divide without any limits, making them effectively immortal.
It may be nature's greatest double-edged sword. Coax cells into producing telomerase, and they will survive indefinitely, but they will also become cancerous.
To safeguard against cancer, adult cells keep track of how many times that they have multiplied, and once they have reached a pre-set limit - often around 80 divisions - they die. Telomerase interferes with this record keeping.
If you can find a drug or gene therapy that interferes with telomerase, it could fight the unchecked growth of cancer cells, said Mark Muller, a cancer researcher who studies telomeres at the University of Central Florida.
"Ninety percent of all cancer cells are telomerase rich," Muller said.
Several companies, including Geron, have started testing drugs that gum up the telomerase enzyme, so that it can't extend the lives of cancer cells.
Telomerase lengthens telomeres, repetitive DNA sequences that sit at the ends of chromosomes. Each segment of a telomere is like a ticket that gives it permission to divide. When cells run out of those credits, they cease dividing.
Geron is developing a modified DNA molecule that gets stuck inside of telomerase, so that it can't build up the ends of telomeres in cancer cells. The company is also working with a vaccine that trains cancer patients' immune systems to attack cells that produce telomerase. In adults, almost all of the cells that produce telomerase are cancerous.
Those cancer treatments took shape almost 20 years after academics made a breakthrough discovery.
In the early 1980's Elizabeth Blackburn, Carol Greider and Jack Szostak identified telomerase and learned how it works. Some scientists speculated people could live longer by using the enzyme to buy extra time for their aging cells, but that idea remains risky and unproven.
"By itself, lengthening telomeres would probably just increase the rate of tumor formation," said Chris Patil, a researcher at the Buck Institute for Age Research in Novato, California. "Experiments with mice have shown that lengthening telomeres extends lifespan, but only if you introduce multiple other mutations to block cancer."
Considering the risks of telomere-extension therapy, he thinks that scientists have bigger fish to fry.
"In the absence of a comprehensive understanding, it's very dangerous," Muller said. "We have to figure out how to do maintenance on our telomeres."
Muller thinks humans could live for 90 to 210 years once scientists know more about the molecular basis of aging.
"If we could figure out how to do maintenance, we could extend our lives," he said. "But it has to be done very carefully, and we'd have to have a comprehensive understanding of the mechanism. "
本年度諾貝爾醫(yī)學(xué)獎(jiǎng)被發(fā)現(xiàn)端粒酶酵素的三位科學(xué)家共同奪得,端粒酶酵素使細(xì)胞無(wú)限分裂,也就是使細(xì)胞長(zhǎng)生不老。
對(duì)細(xì)胞進(jìn)行誘導(dǎo),使之產(chǎn)生端粒酶,這些細(xì)胞會(huì)無(wú)限期的生存下去,但也會(huì)癌變。這也許是大自然最大的雙刃劍。
為預(yù)防癌癥,成人細(xì)胞記錄細(xì)胞分裂的次數(shù),一但達(dá)到八十次左右的預(yù)定極限,細(xì)胞就會(huì)死亡。端粒酶干擾這一記錄過(guò)程。
在佛羅里達(dá)大學(xué)進(jìn)行端粒酶研究的癌癥研究者,馬克*穆勒說(shuō),如果你能找到一種藥物或基因療法,那么就能抵制癌細(xì)胞的過(guò)度增長(zhǎng)。
"百分之九十的癌細(xì)胞都富含端粒酶,"穆勒說(shuō)。
包括杰龍公司在內(nèi)的幾家公司已開(kāi)始進(jìn)行抑制端粒酶酵素的藥物試驗(yàn),使之不能延長(zhǎng)癌細(xì)胞的生命。
端粒是位于染色體末端的DNA重復(fù)序列,而端粒酶使端粒變長(zhǎng)。一個(gè)端粒的每一個(gè)片段就象一張細(xì)胞分裂的通行證。細(xì)胞分裂到預(yù)定的次數(shù)時(shí),就停止分裂。
杰龍公司正在研發(fā)一種經(jīng)修飾的DNA分子,它可附著在端粒酶內(nèi)部,使之不能在癌細(xì)胞內(nèi)延長(zhǎng)端粒末端。該公司還在研發(fā)一種疫苗,這種疫苗訓(xùn)練患者的免疫系統(tǒng)去攻擊產(chǎn)生端粒酶的細(xì)胞。在成年人中,幾乎所有產(chǎn)生端粒酶的細(xì)胞都是癌細(xì)胞。
在學(xué)術(shù)上突破性發(fā)現(xiàn)二十年之后,才形成這些癌癥療法。
上世紀(jì)八十年代初,伊利莎白*布拉克本、卡洛*格雷德及杰克*紹斯塔克三人識(shí)別出端粒酶,并了解其作用原理。有些科學(xué)家推測(cè),用這種酶為正在老化的細(xì)胞贏得多余的時(shí)間,這樣可以延長(zhǎng)人的壽命。但這種想法是危險(xiǎn)的,也未被證實(shí)。
"僅僅延長(zhǎng)端?赡苤粫(huì)增加腫瘤形成率,"在位于美國(guó)加利福尼亞州的巴克老年研究所工作的研究員,克麗絲* 帕蒂爾說(shuō),"白鼠試驗(yàn)已表明,只有在導(dǎo)入成倍的其它突變阻止癌癥的情況下,延長(zhǎng)端粒才會(huì)延長(zhǎng)壽命。"
因?yàn)檠娱L(zhǎng)端粒療法具有危險(xiǎn),他認(rèn)為還有更大的問(wèn)題需要科學(xué)家去解決。
"在缺乏全面了解的情況下,用延長(zhǎng)染色體端粒的方法來(lái)延長(zhǎng)壽命是極其危險(xiǎn)的,"穆勒說(shuō),"我們必須知道如何保養(yǎng)我們的端粒。"
穆勒認(rèn)為,科學(xué)家進(jìn)一步了解了衰老的分子基礎(chǔ)之后,人類(lèi)就能活到九十到二百一十歲。
"如果明白如何保養(yǎng),我們就能延長(zhǎng)壽命。但這樣做必須慎之又慎,還必須對(duì)其機(jī)理有全面的了解。"穆勒說(shuō)。