The Future Looks Bright for Genetic Medicine

Today, gene therapy, genomics, and stem cell therapy are considered to be discrete fields of research.

Nov 22, 2004
Ronald Crystal

Courtesy of Ronald Crystal

Today, gene therapy, genomics, and stem cell therapy are considered to be discrete fields of research. I believe that within 20 years, these three fields will team up to form a new medical specialty: genetic medicine.

These worlds are going to come together because they have so much to offer one another. Genetic transfer will be useful for instructing stem cells to differentiate, and it may enhance their therapeutic potential or control their possible side effects. Stem cells may be the ultimate vehicle to deliver genetic therapy, solving many of the problems that hamper current vectors. Stem cells home to a specific organ, and thus may be able to carry a gene to a specific target, without the immune system activation that can occur with viral vectors. Genomics may supply the specific data to both engineer and control stem cells, thus providing the underpinnings of genetic therapy.

When these three pieces join forces, it may be possible to treat and prevent human disease as never before. In my vision for the future, doctors in genetic medicine will have their own subspecialty as do pulmonary doctors, cardiac surgeons, and transplant surgeons. The development of these new technologies, however, will take time.

I think we will see in the next several years that gene therapy and stem cell therapy will continually move to the clinic, but we should expect some failures as well as partial successes. Setbacks will send us back to the laboratory. The field of gene therapy has seen obstacles in the past, and the consequences have raised the regulatory bar. Nonetheless, the field of gene therapy is vigorous.

I am currently conducting a clinical trial and I am planning three others within the year in humans. As more successes accumulate, everyone will recognize that this is going to work. Then we will see investors and pharmaceutical companies pouring their funds into genetic medicine.


I started a company 11 years ago called GenVec, which was formed during a time of high excitement about gene therapy. I am no longer involved in the company, but what I see happening with stem cells now is similar to what was happening with gene therapy in the early 1990s. It is now recognized that these are good ideas, but translating these good ideas into therapies is a lengthy process. Plenty of parallels can be found in the history of medicine: In vitro fertilization, cardiac surgery, monoclonal antibodies, and organ transplantation all took many years to develop.

The enormous potential of new technologies tends to generate excitement in scientists, the media, and the public. But gene therapy, and by extension stem cell therapy, are essentially drugs. Stem cell therapy and its commercialization will happen, but I think about the coming challenges in developing a working drug. Not only do scientists need to create stem cells, but they also have to convert them into specialized cells: pancreatic islet cells for diabetes, myocardial cells for heart failure, or neurons for Alzheimer disease or spinal cord injuries. Once the cells differentiate into a multitude of cell types, they need to make all the right connections, be in the proper orientation, and be present in the correct numbers.

Gene therapy and stem cell therapy have produced spectacular results in tissue culture and animal models, but translating that to the clinic is complex. Pharmaceutical companies know that all too well: It can take 15 years to develop a small molecule and get it to the clinic, and it can cost in the neighborhood of a billion dollars.

Though commercially viable, putting these ideas into practice may require a time line that is too long for some investors. In the world of venture capital, the structure demands a return within a reasonable amount of time, whether it is three years or five years, and this is appropriate. Investors put funds into biotech companies rather than a huge company such as General Motors because they are willing to take bigger risks, and so they should get bigger returns. The problem is the time needed to bring a drug to market. Investors look for products that are closer to reality or closer to the clinic.

This is one of the most exciting times in biologic sciences. Not only do we have the genome, but we also understand genes and gene translation, and we are working on transforming that into monoclonal antibodies, small-molecule designer drugs, and stem-cell therapies. This leads to important questions for our society. How do we move this research into the clinic in an era in which venture capitalists and other investors want a reasonable time for return on their money? Also, how do we put into practice the therapies that make sense in terms of the costs of medical care?


In academic work, you are given resources and you are expected to give something in return. Society expects scientific knowledge, and the mechanism by which it is achieved is grants. You get a good idea, you get a grant, and then you investigate that idea for three or four years. Then you get another good idea and get another grant.

In biotech, it's different. The funding mechanism is venture capital, and you sometimes don't get as many shots on goal as you do in academia. In the biotech world you have to be successful or you will not get another chance, because you will not be able to attract the funds. It's harder conceptually. You are often making decisions when you don't have all the information available. You know something works in mice, but you do not know if it's going to work in humans. Yet, you have to make a decision. Are we going to test a drug in humans? Are we going to use a cell line that's going to take years to get approval from the FDA? Should we use that virus or make that monoclonal antibody? All these processes require big investments, and once you make such a decision you can't go back. It's a very challenging environment; my experience in biotech was terrific and I would do it again.

In the academic world, you are surrounded by the right people who create a challenging intellectual environment. The same thing is true in biotechs. Intellectual ferment thrives, but in this case it's the venture capitalists and the CEOs who impart a different way of thinking or of looking at a problem.

Between the worlds of biotechnology and academia the mechanisms are in place to fund genetic medicine. It's a challenge to move into the clinic; you have to be creative. A variety of strategies can be used to fund this research, including traditional funding mechanisms such as the National Institutes of Health and funding agencies in Europe, which are now joined by philanthropy and businesses in south Asia.

Ultimately, genetic medicine will be successful, and a day will come when a lack of funding will be a thing of the past.

Ronald Crystal is a professor and chair of the Department of Genetic Medicine at Weill Medical College of Cornell University, as well as the chief of pulmonary and critical-care medicine at Weill Cornell-New York Presbyterian Hospital. He was the first to use recombinant virus as a vehicle for in vivo gene therapy. He has published more than 600 scientific articles, edited several textbooks, and holds several biomedical patents.

He can be contacted at