自從複製羊 Dolly 問世以來，引起社會各界人士的注意。由基因工程所引發之宗教、道德、生態等問題受到越來越多人的關注。在這裡我談談自己所瞭解的基因工程，供各位做個參考。
基因是細胞核中一種傳遞遺傳訊息的物質。人類及其他生物（動植物）按照基因的遺傳藍圖去合成蛋白質、再生細胞及組織。在人的身上存在著大約 7,000~10,000 種基因。其大小及性能均不相同。經過幾十年的研究，人類對其中約 1,500 小的基因的性能與結構有了初步的瞭解。但對那些大的基因，特別是染色體的結構及作用卻瞭解得極少。基因的體積增大，給測定其結構與性能帶來了極大的困難。
染色體及其它基因是由DNA（脫氧核醣核酸）組成。DNA共有四種，通常用字母A（腺嘌吟）、T（胸腺嘧啶）、G（鳥嘌吟）、C（胞嘧啶）表示。染色體就由這四種 DNA 以不同的次序組成長鏈。這種 A、T、G、C 的排列次序稱為一級結構（primary structure），然後，長鏈在空間折合形成二次結構（secondary structure）；二條這樣的長鏈耦合而成雙螺旋形狀。其中一條鏈中的 G 與另一條鏈中的 C 耦合，A 與 T 耦合。人的染色體鏈長度達 30 億個 DNA之多。遺傳密碼就存在於這些 DNA 的排列次序之中。
基因工程即以人為方法重組基因中DNA 的排列次序，但在這麼長的鏈上測定 DNA 的排列次序需要快速經濟的方法。但現在能夠應用的方法－－電泳走膠法，卻無法提供那樣的速效，而且成本很高，無法給人類提供足夠的基因結構信息。例如：大腸桿菌基因中的 DNA 鏈長約為百萬個，但它的 DNA排列次序的測定卻花了12 年。因此快速地測定基因中 DNA 的排列次序成為遺傳學是否能深入的關鍵；否則人類就無法理解遺傳機理，基因工程就僅僅建立在薄冰之上。在這種情況下，美國科學界在國會的支持下，集中了大量的資訊及基因結構的測定，這就是 Human Genome Project (HGP) 的科研計劃。除了改進電泳走膠法外，HGP還投資發展各種新的 DNA 分析方法。幾種新的質譜技術；例如 MALDI-TOF 和 FTMS 在這種情形下得到了發展，並且能用於測定小的 DNA 鏈段。但在 DNA 鏈長超過 200 個時，這些方法都陷入困難。首先是信號的靈敏度迅速降低，使得分辨率迅速降低，測定的準確性漸漸消失。雖經多年的努力試圖改進，但至今無法突破。另一方面，電泳走膠法改進的進展，在這幾年中也很有限。總之，到目前為止，由於不瞭解染色體及基因結構與性能，人類對遺傳機理的知識是極其有限的。
一）染色體和基因中 DNA 排列結構的測定。這一方面的工作主要是政府投資，作為國家的一項長期發展項目。但許多企業也在積極參與，因為擁有測定技術的專利權將會帶來巨大的利潤。幾年前，有許多有關這方面技術進展的報道，最近漸漸冷下來了。因為大家都意識到問題的複雜性，並不是很快能夠解決的。在這方面總體的進展很有限。
作者簡介：朱逸飛博士，中國浙江省杭州市人。畢業於中國杭州大學並任教數載。1993年於美國印第安那州普度大學取得化學博士學位後，就職於田納西州Oak Ridge 國家實驗室。1997 年10月來萬佛城任義務教師。
Since the birth of the duplicated sheep “Dolly,” genetic engineering (GE) has attracted attention from all levels of society. GE raises questions of religion, ethics, and ecology that are of great concern to many people. I would like to share a little of my understanding of GE, hoping that it will be helpful to everyone here.
What Are Genes?
Genes are the substance within the nucleus of a cell that transmit genetic codes. In human beings and other bio-species, the synthesis of protein and the reproduction of cells and tissue take place according to the genetic blueprint contained in the genes. There are approximately 7,000 to 10,000 kinds of genes of differing sizes and properties in the human body. After several decades of research, people have gained a preliminary understanding of the structure and properties of about 1,500 small genes. However, knowledge of large genes, especially chromosomes, is very limited. The larger the gene, the more difficult it is to determine its structure and properties.
Chromosomes and other genes are composed of DNA. There are four types of nucleotides (DNA building blocks) labeled A, T, G, and C [according to the four types of nitrogenous bases occurring in the nucleotides, namely, adenine, thymine, guanine, and cytosine]. These four types of nucleotides combine in different sequences to form long chains. The sequencing of A, T, G, and C nucleotides is called the primary structure. The twisting of the long chains is called the secondary structure. Pairs of long chains couple together in a double helix structure. The G in one chain couples with the C in another chain, and the T in one chain couples with the A in another chain. A human chromosome can be as long as 3 billion nucleotides. The genetic codes are stored in these DNA sequences.
What Is Genetic Engineering?
Genetic engineering aims to re-arrange the sequence of DNA in gene using artificial methods. To determine the DNA sequence on such a long chain, a high-speed, low-cost method is needed. Unfortunately, the currently available method (gel-electrophoresis) does not satisfy these requirements. It cannot provide sufficient information about the genetic structure. For example, the DNA chain in the gene of E. coli is approximately one million nucleotides long. Its DNA sequence analysis took 12 years. Thus, high-speed determination of DNA sequence in genes is critical to the development of genetics. Without such a technique, it will be impossible to understand the genetic mechanism, and GE will be built on thin ice. Given this predicament, the scientific community, supported by the U.S. Congress has delegated substantial resources to be used in determining gene structure under the auspices of the Human Genome Project (HGP). In addition to improving the gel-electrophoresis method, HGP has also invested a huge amount of capital in supporting the discovery of a new method for DNA analysis. Several new mass-spectroscopic techniques, such as MALDI-TOF (matrix-assisted laser desorption and ionization - time-of-flight mass spectrometer) and FTMS (Fourier transform mass spectrometer), have been developed and applied to analyze the DNA segment. However, these methods run into difficulties when the DNA segment is larger than 200 nucleotides. As the size of the DNA increases, the sensitivity and resolution of the signal greatly decreases and analysis using these methods gradually becomes unreliable. To date this difficulty has not been overcome despite intensive research. What is more, the method of gel-electrophoresis has seen little improvement in recent years. Due to the overall lack of information about gene structure, our knowledge of the genetic mechanism is very limited.
The Current Stage of Genetic Engineering
With every new scientific discovery, there are always those who use it to seek profit. The field of genetics is no exception in this matter. Investors began getting into GE business several years ago. What is the current stage of development of GE? Roughly, it can be seen in three major fields. 1) The determination of DNA sequence in chromosomes and other genes. Work in this field is mainly supported by the U.S. government, which considers long-term development to be of national interest. Many private industrial enterprises are also extensively involved, since the patent owner of such an analytic technique will reap a huge return. Several years ago, there were many reports on developments in this field. The excitement has gradually subsided because scientists have realized the complexity of the problem. This problem is not going to be solved in the near future. There has been very little overall advance in this field during the past several years. 2) Artificial horizontal gene transfer--a synthetic method of gene transfer between different species. Since the structure and function of some small genes are relatively well known, biologists try to transfer these genes to other bio-species to improve their functions. Private enterprises have actively been testing this method on animals and vegetables in order to obtain “super products.” Goverment-supported research institutes mainly use horizontal gene transfer to obtain knowledge about the genetic mechanism. Since the genetic mechanism is a very complicated system, they can mostly conduct blind tests by means of horizontal gene transfer. There are many unknown factors in this field, regardless of whether the method used is direct insertion of genes or simple mixing of genes. The probability of success is very small, and only a few products exist. The possible side effects of these GE experiments are still unclear. There has not been much successful advance in this field. 3) Cloning. “Dolly” is a sheep genetically duplicated using a complete set of chromosomes from an adult sheep. This success was based on a large number of failures. But scientists have not been able to repeat it. The validity of scientific results is based upon their reproducibility. Since the experiment has not been repeated, many people doubt its validity. About 50% of the scientific community is not convinced by the result. It would be extremely difficult to clone a human being even in the absence of pressure from social objections.
Why We Study Genetic Engineering
What benefit could GE bring to humankind? Some scientists believe that, since genetic codes determine the appearance, personality, health, and aging process of human beings, if that genetic information in the chromosomes could be decoded and the genetic mechanism were understood, we could potentially control and improve our health, quality of life, and the biochemical processes in our bodies. In other words, we could control our own fate. Also, we’d be able to improve the genes of other animals and vegetables so that they could serve humankind better. At first sight, these ideas seem reasonable and attractive. However, careful analysis reveals that they are based upon an incorrect theory--the theory of gene determinism.
To be continued
About the author: Dr. Yifei Zhu is from the city of Hangzhou, Zhejiang Province of China. He graduated from the University of Hangzhou in China and taught there for a few years. After earning his doctorate degree in chemistry from Purdue University in Indiana in1993, he worked for Oak Ridge National Laboratory in Tennessee. In October 1997 he came to the City of Ten Thousand Buddhas to serve as a volunteer teacher.