Biotechnology – Past, Present, And Future

By

Dr. Hwa A. Lim, Ph.D., MBA

Chairperson & CEO, D’Trends, Inc., Silicon Valley, California, USA

hal@dtrends.com

 

₪ “All Darwin asked of people in his “survival of the fittest” was that they compete for their own life.  The new cosmology asks that people be the creator of life.” – Julian Huxley, 1953. ₪

Humanity’s Top Ten

At the Fifth APEC R&D Leaders’ Forum, March 11, 2004, Christchurch, New Zealand, Alan G. MacDiarmid of the University of Texas at Dallas and 2000 Chemistry Nobel Laureate, in his lecture “The World Is Becoming Smaller”, reminded the audience that the world population in 2003 was 6.3 billion, and by 2050, the world population would be 10 billion.  At minimum we will need the equivalent of 150 million barrels of oil per day from some new clean energy source by then.  Where will we get it?  For worldwide peace and prosperity we need it to be cheap.  We simply cannot do this with current technology.

Energy, of course, would not be the only challenge.  He listed the following as humanity’s top ten challenges for the next fifty years: 1) Energy, 2) Water, 3) Food, 4) Environment, 5) Poverty, 6) Terrorism & war, 7) Disease, 8) Education, 9) Democracy, and 10) Population.  Needless to say, our best hope of overcoming these challenges is with new technologies.  Biotechnology is one of them.

Old, New And Future Biotechnology

In the past few decades, breakthroughs in biotechnology have been reported with increasing regularity not only in peer-reviewed journals and respectable newspapers, but also in tawdry tabloids.  This undoubtedly leads to the misconception that biotechnology is something very new.  Few, if any, of us would associate the use of microorganisms to ferment foods during the dawn of civilization thousands of years ago with biotechnology.

In the present era, this “old biotechnology” has been instrumental in the development and implementation of processes for the manufacture of antibiotics and other pharmaceuticals, industrial sugars, alcohols, amino acids and other organic acids, foods, and specialty products through the application of microbiology, fermentation, enzymes, and separation technology.  Within remarkably short periods, engineers, entrepreneurs, and attorneys working with life scientists, often achieve scale-up to industrial production.  This led to the growth of the pharmaceutical, food, agricultural processing, and specialty-product sectors whose annual sales exceeded $100 billion in the U.S. alone in the early 1990s.

Table 1.  Selected milestones in the history of genetics and biotechnology.  (Table adapted from D. Suzuki, and P. Knudtson, Genethics, (Harvard University Press, Massachusetts, 1990)).

 

The “new biotechnology” started in the early 1970s with direct manipulations of the cell’s genetic machinery through recombinant DNA techniques.  Its application on an industrial scale since 1976 has fundamentally expanded the utility of biological systems.  Scientists and engineers can now confer new characteristics to microbes, plants and animals by changing the genetic make-ups.  Just like inanimate matters, some biological molecules can now be biologically manufactured or biofactured.  The new biotechnology, combined with the existing industrial, government, and university infrastructure in biotechnology and the pervasive influence of biological substances in everyday life, has set the stage for unprecedented growth in products, markets, and expectations.  To date, the principal impact of the new biotechnology has been in the pharmaceuticals arena, but the scope has been expanding.

Mother Nature, Father Time

For eons, human beings have been remaking Mother Nature.  Until about forty years ago, however, human attempts have been tempered by the restraints imposed by species boundaries.  Humans crossed close relatives of the plant or animal kingdoms to create new breeds.  It took a long historical process of tinkering with trials and errors to create new agricultural products, new sources of energy, more durable building materials, life-saving pharmaceuticals, and other useful products.  Mother Nature dictated the terms of engagement in all these cases.

The growing repertoire of tools from “new biotechnology” makes it possible to perform radical experiments on Mother Nature’s life forms.  In other words, modern biotechnology can author Mother Nature by shortening Father Time.  We are the author of new life-forms.  We are now experimenting with Mother Nature in ways never before possible, creating unfathomable new opportunities and concurrently, potentially generating grave new risks for the environment.

From Green Revolution To AgBiotech Revolution

The Green Revolution of the 1960s depended on agrochemicals and achieved a doubling of production with only a 10%–20% increase in the amount of land under cultivation.  The world population is exploding, while one third of all crops are still lost to pests and diseases.  As the world population rises to 10 billion over the 21^st century, the Green Revolution will soon reach its saturation point.  Its impact on the environment is also increasingly unacceptable.

Sir Robert May, chief scientific adviser to the British government, warned, “…we will not be able to feed tomorrow’s population with today’s technology.  We will now need to create crops that are shaped to the environment, with biotechnology, whereas before, with the Green Revolution, our environment was shaped by crops that were created with the use of chemicals derived from fossil fuels.”  Sir May emphasized the Green Revolution was mainly publicly-fund, whereas genetic modification is all being done with private money.   Farmers and agribusiness are seen as the chief beneficiaries of the new technology.  What is required is a reorientation through public-private partnerships.

Unlike petrochemicals, genetically modified organisms (GMOs) are alive.  Therefore, GMOs are inherently more unpredictable than petrochemicals in the way they interact with other living organisms in the environment.  Once released, accidentally or otherwise, it is virtually impossible to recall GMOs back to the laboratory, especially those that are microscopic in nature.  The general consensus is the public will eventually accept genetically modified foods, thereby ending hostilities.  However, science must offer something of value, such as improved nutrition via functional food.  Just making life easier for farmers with pest-resistant crops will not outweigh real or imagined risks to the public.

Metabolic or nutritional genomics is using genetic engineering to improve nutritional value of plants.  Rice, though a staple food for half the world’s population, is a relatively poor source of many essential nutrients, including vitamin A and iron.  An estimated 124 million children worldwide are deficient in vitamin A, and a quarter million in Southeast Asia go blind each year because of the deficiency.  Improved nutrition can prevent 1 to 2 million deaths a year.

At the International Rice Research Institute (IRRI), Zurich’s Federal Institute of Technology (ETH), Ingo Potrykus and his colleague, Peter Beyer of the University of Freiburg, Germany, have succeeded in splicing three genes into rice to make it iron-enriched and four other genes to make it rich in b-carotene, a source of vitamin A.  The iron-enriched rice and vitamin A-enriched functional rice are combined by crossing.  The new crop, dubbed “golden rice” because of the hue the b-carotene gives to it, is not expected to be available to farmers for several years.  Nevertheless, IRRI is heading in the right direction of functional foods and is already working on breeding the new trait into popular varieties.

From Fishing To Aquaculture

A 1997 United Nations estimate indicates that the supply of seafood products would have to increase seven-fold to meet the worldwide requirement for fish and other seafood by the year 2020.  Given the rapid decline in world fish stocks, caused mainly by over fishing, it is clear that demand can only be met by aquaculture.

Worldwide aquaculture production of many fish species faces several challenges.  Among them are the selection and supply of suitable broodstock, growth rate, feed conversion efficiency, feeding costs, control of the reproductive cycle, and disease protection.  Traditionally, the broodstock is selected by cross breeding to enhance the fishes’ desired traits.  Cross breeding is generally time-consuming and traits are slow to emerge and unpredictable.  Gene transfer technology – identifying genes responsible for desirable traits using molecular biology and then transferring them to the broodstock – is an improvement over traditional selection and breeding methods.  New traits not present in a genome can also be genetically transferred into an unrelated species, enabling the production of new and beneficial phenotypes.  The technology, transgenesis, has been making major inroads in aquaculture.  It has enhanced growth rate, increased production efficiency, improved disease resistance and expanded ecological ranges.

Roughly half of the operating costs in fish farming are related to feed.  Thus the major concerns for the industry are the growth rate and feed conversion efficiency of the cultured fish species.  Robert Brinster and co-workers of the University of Pennsylvania succeeded in creating a “supermouse” roughly twice the size of its littermates.  Following the work, Zhoyan Zhu and colleagues at the Institute of Hydrobiology, Wuhan, China, used the mouse metallothionein promoter to produce the first transgenic fish.  Since then, several laboratories have reported successful production of faster growing fish in several species.  Recently, transgenic tilapia with a two-fold increase in growth rate has also been produced.

Transgenesis appears to be a viable approach in generating faster growing fish.  The magnitude might, however, depend on the species, the nature and strength of gene constructs, and the number and location where the transgene is incorporated in the host DNA.  This brings us to a major concern in producing transgenic fish for human consumption – the consumer’s perception of food safety.

A way to ensure safety is to only use DNA and genes from fish species to make the DNA constructs.  A form of “all-fish” gene construct based on the antifreeze protein gene promoter from the ocean pout linked to the Chinook salmon growth hormone gene has been used to produce transgenic Atlantic and Pacific salmon.  The constructs are “all-fish” because the genes are from one fish to another.  In these cases of the transgenic Atlantic and Pacific salmons, essentially the fishes’ growing seasons have been extended into colder months, and thus they show higher growth rates.  The dramatic increase in growth enhancement is on average 3 to 5 folds, with some individual fish being 10 to 30 times larger in the early phase of growth.  Subsequent generations of these transgenic fish have been produced.  These fast growing fish are fully capable of entering full strength seawater as smolts almost a year earlier than their non-transgenic siblings.

Farmers, Pharmers And Pharmas

There are many other actively researched biotech areas.  But a recurring confusion is the boundary between biotechnology and pharmaceutical industry.  To be fair, the boundary is fuzzy.  After all, of the more than 300 publicly traded biotechnology companies, Amgen ($69 billion in capitalization) and Genentech ($55 billion in capitalization), both in California, account for about a third of the market capitalization.  The next most valuable company, Biogen Idec, has a market capitalization of $21 billion.  Genentech, which essentially started the biotechnology industry with its founding in 1976, introduced three drugs in 2003.  Chief among them is Avastin for cancer treatment.  Amgen, founded four years after Genentech, has relied on its two runaway multi-billion-dollar blockbusters introduced around 1990: Epogen, a red blood cell booster to treat anemia; and Neupogen, a white blood cell booster to treat a side effect chemotherapy.

Generally speaking, biotechnology companies have concentrated on using genetic engineering to make proteins that can be used as drugs.  Pharmaceutical companies, on the other hand, tend to rely more on drugs made from chemicals.  Genentech, for example, licensed a cancer drug Rituxan from Idec Pharmaceuticals in 1995.  Rituxan, which is now being tested to treat rheumatoid arthritis, is a type of protein called monoclonal antibody.  Monoclonal antibodies have since become a mainstay of the industry.

Chemical small molecule drugs made by big pharmaceutical companies can be more convenient at times because they can be taken as pills, while proteins must be injected because they would be destroyed by the human digestive system.  Moreover, for some purposes, such as blocking certain protein inside cancer cells, small molecules are necessary.

Producing protein drugs through current manufacturing process means building factories that can cost over $100 million.  Pharming, using farm animals as drug factories, will require less capital outlay.  The animal process is currently not that fast and cheap yet.  Researchers must first harvest the female animal’s eggs, fertilize them in vitro and implant human genes into these embryos to produce the desired therapeutic proteins.  The transgenic embryos must then be transplanted into surrogate mothers, who would give birth to the animals – the founder herd.  Once they grow to adulthood, the animals that produce the highest concentration of the desired drugs in their milk are bred to make a herd.  In short, these transgenic animals are being groomed as four-legged drug factories.

Cloning, combined with genetic engineering techniques, suggests that ordinary barnyard animals might someday be transformed into walking four-legged organ factories in a process called xenotransplantation.  In xenotransplantation, hidden diseases may be transferred from the animal to humans along with life-saving organs.  Medical experts insist that while such concerns must be taken seriously, cloning offers one of the few practical solutions to the critical problem of organ shortages.

Stem cells are sometimes called magic seeds since they possess the ability to replicate indefinitely and morph into any kind of tissue found in a human body.  They are nature’s blank slates, capable of developing into any of the nearly 230 cell types that make up the human body.  Potential uses of stem cells are immense.  Of note are first, stem cells can be used in delineating the complex events during human development; second, stem cells can be used in the biotechnology and pharmaceutical industry to streamline drug safety tests; and third, stem cells can be used in cell and tissue therapies, and organ transplants.  Scientists believe they will lead to cures for debilitating diseases once thought untreatable.

The Year 2050

Now let us go back forty years into the future.  By 2050, the world population will be 10 billion.  Ten billion is 10¹⁰, it is a very nice number written out in Arabic numerals, but more importantly, it is a very large number.

Figure 1. The Earth at night.  (Credit: C. Mayhew and R. Simmon of NASA, November 27, 2000).

 

This is what the Earth looks like at night, occupied by 6.3 billion people.  Human-made lights highlight particularly developed or populated areas of the Earth’s surface, including the seaboards of Europe, the eastern United States, and Japan.  Many large cities are located near rivers or oceans so that they can exchange goods cheaply by boats and ships.  Particularly dark areas include the central parts of South America, Africa, Asia, and Australia.  But this image does not tell the whole story.  Most of the world’s additional people will be born in the poorest places, more or less coinciding with the particularly dark areas.  To support the growing population, land will be slashed and burnt to grow food.  Developed nations will, on the other hand, pay an ironic price for affluence – more and more people will live far longer and therefore require unprecedented medical care on a scale increasing beyond those countries’ means.

Whether we are in developing or developed nations, may be we should all wake up and stop fighting against each other.  We should instead change our focus and concentrate our resources to work on these imminent issues – the humanity’s top ten.

About The Author

Hwa A. Lim, aka Hal, scuba diving in the Red Sea to check out the flora and fauna.

Dr. Hwa A. Lim, Ph.D. (science), M.A. (science), and MBA (strategy and business laws), B.Sc. (Honours), ARCS, is a Kingstone Best-Seller author, author of fourteen titles in English, and a regular contributor to Symbiosis.  Hal is credited with coining the neologism “Bioinformatics” in 1987, establishing and shaping the field, and initiating the world’s very first bioinformatics conference series.  These credits earn him the title “The Father of Bioinformatics”.  He has served as a bioinformatics expert for the United Nations to help set up biotech research parks, and as a review panelist for United States federal agencies, and as a consultant for prominent biotech, pharmaceutical and healthcare companies, organizations, and governments.  He has the distinction of being a key member of two separate teams that took two distinct companies IPO in the United States.

Hal is an articulate and well sought-after speaker at international meetings.  This article is based on some of his lectures, from parts of two of his books, CHANGE and Sex Is So Good, Why Clone? (EN Publishing Inc., Santa Clara, California, 2004).  Hal, Chairperson and CEO of D’Trends, Inc., resides in Silicon Valley, California, USA.  He can be reached at hal@dtrends.com, http://ww.dtrends.com/HAL.html/